Synthesis and heterocyclization of triterpenic 1,3-diketones

DOI httpsdoiorg1024820ark5550190p011344 copyAUTHOR(S)

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Organic Chemistry

Arkivoc 2020 part __ 0-0

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Synthesis and heterocyclization of triterpenic 13-diketones

Mikhail A Nazarov Irina A Tolmacheva and Victoria V Grishko

Perm Federal Scientific Centre Acad Korolev St 3 614013 Perm Russia

Email tolmairgmailcom

Received mm-dd-yyyy Accepted mm-dd-yyyy Published on line mm-dd-yyyy

Dates to be inserted by editorial office

Abstract

Procedures for the synthesis of some new lupane and 18αН-oleanane pyrazole and isoxazole derivatives from

betulin are reported The synthetic scheme for the preparation of 12-azoles involves aldol condensation of

triterpenic aldehydes with acetone as a key stage

Keywords Triterpenoids aldehydes aldol condensation 13-diketones pyrazoles isoxazoles

Arkivoc 2020 part _ 0-0 Nazarov MA et al

Page 2 copyAUTHOR(S)

Introduction

The strategy for the design of hybrid molecules including those from natural compounds is based on the

methods of modern organic and medicinal chemistry and provides the preparation of chemical entities with

two (or more than two) structural domains with different biological functions1 In accord with the molecular

hybridization concept heterocyclic modification of triterpenic skeleton can provide new hybrid molecules with

high biological potential and bioavailability2-5 Concurrently β-dicarbonyl compounds have shown themselves

as useful building blocks for the construction of heterocycles with one two or more heteroatoms6-8 So 13-

diketones obtained from 3-oxo derivatives of allobetulin betulinic dihydrobetulonic 23-hydroxybetulinic

oleanolic maslinic and glycyrrhetinic acids were successfully used as convenient and promising objects in the

synthesis of NO-based five-membered heterocycles such as pyrazoles oxazoles and isoxazoles condensed

with triterpenic skeleton at the 23-position9-19 Herein we describe a convenient synthetic route for the

preparation of lupane and oleanane 13-diketones with use of the aldol condensation Further

heterocyclization of the synthesized triterpenic 13-diketones to derivatives with a 12-azole fragment

(pyrazole and isoxazole) in A or E cycles of triterpenoid has also been evinced as possible

Results and Discussion

Betulin 1 and its derivatives ndash 328-betulin dibenzoate 2 328-betulin diacetate 3 allobetulone 4 and betulinal

5 ndash were used as easily available starting compounds for the synthesis of new triterpenic 13-diketone

derivatives First via αβ-unsaturated aldehyde intermediates 6 7 920-23 compounds 2-4 were converted to β-

hydroxyketones 10-12 according to the antecedently described method2023 (Scheme 1)

The aldol reaction of compounds 10-12 with acetone was discontinued at first signs of the formation

(TLC) of a crotonrsquos by-product produced by the water elimination of their β-hydroxy ketone fragment In turn

the aldol condensation of betulinal 5 with acetone carried out at room temperature and using t-BuOKminust-BuOH

led to the formation of a new αβ-unsaturated methyl ketone 13 as a single product in an excellent 80 yield

The 1H NMR spectrum of αβ-unsaturated methyl ketone 13 showed CH3-33 protons of the methyl ketone

moiety recorded as a singlet at 227 ppm The E-configuration of the С-28 ndash С-31 double bond was confirmed

by a large coupling constant (165 Hz) between two olefinic protons at 616 and 707 ppm The signals of С-28

С-31 carbon atoms and carbonyl group were observed in 13C NMR spectrum of compound 13 at 13019

14962 and 19858 ppm respectively

The different location of aldehyde group in the structure of compounds 5-9 enabled the introduction of

a 13-diketone fragment at C-2 C-28 and C-30 positions of the triterpenic core According to TLC chromium

(VI) oxide in anhydrous pyridine normally used as an oxidation reagent was not suitable for β-hydroxy

ketones 10 and 11 because in both cases the reaction proceeded with the formation of a multicomponent

hard-to-separate product mixture Lupane 13-diketones 14 15 were obtained in 30 yields by treating

compounds 10 and 11 with PCC in anhydrous CH2Cl2 or with the Jones reagent in acetone (Scheme 2) 18αH-

Oleanane 13-diketone 16 was obtained by oxidation of β-hydroxy ketone 12 with the Jones reagent (other

oxidizing systems failed to lead to a good result)



Scheme 1 Synthesis of triterpenic β-hydroxy ketones 10-12 and αβ-unsaturated methyl ketone 13 from

betulin 1

Lupane 13-diketones 14 and 15 are completely enolized at the C-30 atom that was confirmed by the

data of 1H and 13C NMR spectra with characteristic signals (1) a singlet of protons H3-33 at 211-212 ppm and

a signal of the carbon atom C-32 at 19313-19317 ppm were assigned to the methyl ketone fragment (2) a

singlet of enol hydroxyl in the downfield area at 1565-1567 ppm and a signal of proton H-31 at 585-587

ppm were identified as an enol fragment Two enol forms A and B for 18αH-oleanane 13-diketone 16 in

solution at the ratio 73 were registered on the basis of the integrated intensity of the signals of protons H3-34

(194 and 213 ppm) and proton H-19 (353 and 354 ppm) as well as the proton of enolic hydroxyl (1563 and

1570 ppm) in the 1H NMR spectrum Lupane 13-diketone 17 was obtained by the Claisen condensation of

αβ-unsaturated methyl ketone 13 with HCOOC2H5 in 65 yield (Scheme 3) The enolization of the ketone

group C-34 of compound 17 was confirmed by the registration of doublet signals of olefinic protons Н-28 and

Н-31 (597 and 719 ppm) and protons H-33 and H-34 (557 and 846 ppm) a signal of carbonyl atom carbon C-

32 at 18299 ppm and a signal of C-34 atom at 18252 ppm in the 1H and 13C NMR spectra



Scheme 2 Synthesis of triterpenic 13-diketones 14-16

Scheme 3 Synthesis of triterpenic 13-diketone 17

To obtain pyrazole derivatives compounds 14 16 17 were heated with hydrazine hydrate in an

alcoholminusacetic acid mixture (11) for 15 h (Scheme 4)

The 1H NMR spectra of compounds 18 and 19 showed the presence of two singlet signals at 228 and

612-623 ppm which conjointly with a broad signal at 820-822 ppm were assigned to protons Н3-6prime Н-4prime and

the proton of NH group of a substituted pyrazole cycle respectively whereas the 13H NMR spectra revealed

the characteristic signals of heterocyclic fragment at 10202-10262 and 14125-14712 ppm In the 1H NMR

spectrum of compound 20 the signals of H-4 and H-5 protons of the pyrazole fragment were recorded as two

doublets at 633 and 749 ppm with a coupling constant of 17 Hz and the NH proton signal at 579 ppm The

treatment of triterpenic 13-diketones 14 16 with hydroxylamine hydrochloride in aqueous EtOH in the

presence of CH3COONa at reflux afforded isoxazole derivatives 21 22 in 86 and 73 yields respectively

(Scheme 5) In the 1H NMR spectra of the compounds 21 and 22 the characteristic singlet signals of protons

Н3-6 and Н-4 of isoxazole fragment were recorded at 230-231 and 612-661 ppm respectively



Scheme 4 Synthesis of triterpenic pyrazoles 18-20

Scheme 5 Synthesis of triterpenic isoxazoles 21 22



Conclusions

Triterpenic derivatives with a pyrazole or isoxazole fragment in the A or E cycle of triterpenoids were

synthesized from the lupane and 19β28-epoxy-18αH-oleanane 13-diketones obtained from commercially

available pentacyclic triterpenoid betulin The synthetic route to triterpenic 12-azoles involved the reaction of

aldol condensation of α β-unsaturated aldehydes with acetone the products of which as β-hydroxyketone

and methyl ketone were converted to 13-diketones whose participation in reaction with hydrazine hydrate

and hydroxylamine led to target heterocyclic derivatives

Experimental Section

General The 1H 13C and 2D NMR spectra (HMBC) (δ ppm J Hz) were recorded for solutions in CDCl3 using a

Bruker AVANCE II spectrometer (400 MHz and 100 MHz respectively) relative to HMDS IR spectra (ν cm-1)

were recorded on a Bruker 66S IFS Fourier spectrometer using a thin film obtained by evaporation from the

solution of the substance in CHCl3 Melting points were determined on an OptiMelt MPA100 device at the

heating rate 1degCmin Optical rotation was measured on a Perkin-Elmer 341 polarimeter using sodium D for

CHCl3 solutions at 589 nm Chromato-mass spectra were analyzed using Agilent Technologies 6890N capillary

column HP-5ms 15000 x 025 mm electronic ionization as sample ionization method Thin layer

chromatography (TLC) on ldquoSorbfilrdquo plates was used to control the reaction course and substance purity by

visualization under UV light (254 nm) The samples were then subjected to treatment with a 5 solution of

H2SO4 and heating at 95-100 degC for 2-3 min Column chromatography (CC) procedure was performed using

Macherey-Nagel 60 Silica (0063-02 mm) as an adsorbent For each compound eluents were selected

individually 328-Betulin dibenzoate 2 and 328-betulin diacetate 3 synthesized by treating technical betulin

with an acylating agent (benzoyl chloride or acetic anhydride) in pyridine2124 Betulinal 5 was obtained by

oxidation of the C28 hydroxyl group of betulin by PPC in pyridine25

3β-Hydroxy-28-(2-oxopropylidene)lup-20(29)-ene (13) t-BuOK (4 mmol) was added to a solution of aldehyde

5 (23 mmol) in t-BuOH (50 ml) and acetone (2 ml) The reaction mixture was stirred for 2 h at rt With 10 HCl

added the reaction mixture was extracted with ethyl acetate (30 mL x 2) The organic layer was separated

washed with H2O (5 10 ml) and dried over anhydrous MgSO4 The solvent was evaporated and the residue

was subjected to CC (eluent light petroleumminusethyl acetate 101) Yield 80 mp 1916 degС [] 21

D -240 (с 05

CHCl3) IR (сm-1) 3447 1672 1H NMR (400 MHz CDCl3) δH 707 and 616 (2Н 2d J 165 Hz 28-Н 31-Н) 472

and 460 (2Н 2s 29-Н2) 316 (1Н dd J 51 112 Hz 3-Н) 245 (1Н td J 111 53 Hz 19-Н) 227 (3Н s 33-Н3)

168 (3Н s 30-Н3) 097 095 093 081 074 (15Н 5s 5СН3) 13C NMR (100 MHz CDCl3) δC 19858 15272

14962 13019 11006 7893 5533 5038 5006 4970 4785 4279 4082 3899 3884 3876 3872

3717 3429 3352 2979 2797 2785 2739 2713 2527 2076 1925 1825 1602 1590 1532 1469

MS mz 48035 (M+) Anal Calcd for C33H52O2 C 8244 H 1090 Found C 8261 H 1099

3β28-Dibenzoyloxy-30-oxo-30-(2-oxopropyl)lup-20(29)-ene (14) A solution of 10 (14 mmol) and CH3ONa

(07 mmol) in acetone (100 ml) was cooled to 0-5 degС then the Jones reagent (08 ml) was added slowly with

subsequent stirring of the reaction mixture for 15 min The progress of the reaction was monitored by TLC

The reaction mixture was extracted with ethyl acetate washed with H2O (5 10 ml) and dried over anhydrous

MgSO4 The solvent was evaporated and the residue was subjected to CC (eluent light petroleumminusethyl



acetate 101) Yield 30 mp 1421 degС [] 21

D +184 (с 06 CHCl3) IR (сm-1) 1716 1H NMR (400 MHz CDCl3)

δH 1567 (1Н br s ОН) 805-800 (4Н m Ph) 755-749 (2Н m Ph) 744-738 (4Н m Ph) 587 (1H s 31-H)

579 and 547 (2Н 2s 29-Н2) 469 (1Н dd J 51 110 Hz 3-Н) 453 and 413 (2Н 2d J 111 Hz 28-Н2) 273

(1Н td J 112 54 Hz 19-Н) 211 (3Н s 33-Н3) 107 099 098 090 087 (15Н 5s 5СН3) 13C NMR (100

MHz CDCl3) δC 19313 18530 16686 16622 15162 13286 13262 13100 13042 12953 (2С) 12947

(2С) 12835 (2С) 12825 (2С) 11864 9722 8151 6317 5546 5145 5021 4676 4271 4095 4092

3842 3817 3745 3711 3455 3418 3304 3011 2808 (2С) 2758 2715 2573 2371 2101 1816

1673 1607 1475 Anal Calcd for C47H60O6 C 7830 H 839 Found C 7813 H 854

3β28-Diacetoxy-30-oxo-30-(2-oxopropyl)lup-20(29)-ene (15) A solution of 11 (17 mmol) and CH3ONa (08

mmol) in acetone (100 ml) was cooled to 0-5 degС then the Jones reagent (10 ml) was added slowly with





D +24 (с 059 CHCl3)IR (сm-1) 1733 1H NMR (400 MHz CDCl3)

δH 1565 (1Н br s ОН) 585 (1H s 31-H) 577 and 544 (2Н 2s 29-Н2) 445 (1Н dd J 57 108 Hz 3-Н) 427

and 388 (2Н 2d J 108 Hz 28-Н2) 265 (1Н td J 113 55 Hz 19-Н) 212 (3Н s 33-Н3) 206 and 202 (6Н 2s

2СН3СОО-) 103 095 082 (9Н 3с 3СН3) 083 (6Н s 2СН3) 13C NMR (100 MHz CDCl3) δC 19317 18534

17150 17094 15168 11864 9724 8091 6266 5542 5146 5022 4640 4266 4093 3844 3781

3738 3709 3439 3421 3301 2988 2794 (2С) 2757 2708 2577 2368 2124 2101 2097 1817

1646 1611 1605 1470 Anal Calcd for C37H56O6 C 7446 H 946 Found C 7473 H 912

2-(13-Dioxobut-1-yl)-19β28-epoxyolean-1(2)-en-3-one (16) A solution of 12 (14 mmol) and CH3ONa (095



The reaction mixture was extracted with ethylacetate washed with H2O (5 10 ml) and dried over anhydrous

MgSO4 The solvent was evaporated and the residue was subjected to CC (eluent light

petroleumminusethylacetate 101) Yield 40 mp 1144 degС [] 21

D +27 (с 06) IR (сm-1) 1684 1615 For form A 1H NMR (400 MHz CDCl3) δH 1570 (1Н br s ОН) 792 (1H s 1-Н) 620 (1H s 32-H) 378 and 345 (2H 2d J

78 Hz 28-H2) 354 (1H s 19-Н) 213 (3Н s 34-H3) 116 109 105 102 080 (15H 5s 5CH3) 092 (6H s

2CH3) 13C NMR (100 MHz CDCl3) δC 20297 19688 17662 16363 13117 10035 8788 7125 5221

4673 4600 4481 4158 4148 4104 3956 3673 3627 3451 3292 3271 2877 2867 2658 2641

2628 2623 2452 2186 2107 1951 1883 1615 1329 Anal Calcd for C34H50O4 C 7812 H 964

Found C 7822 H 985

3β-Hydroxy-28-(24-dioxobutylidene)lup-20(29)-ene (17) t-BuOK (4 mmol) was added to a solution of 13 (2

mmol) and HCOOC2H5 (6 mmol) in t-BuOH (50 ml) The reaction mixture stirred for 4 h at rt With 10 HCl

added the reaction mixture was extracted with ethyl acetate The organic layer was separated washed with

H2O (2 10 ml) and dried over anhydrous MgSO4 The solvent was evaporated and the residue was subjected

to CC (eluent light petroleumminusethyl acetate 51) Yield 65 mp 1530 degС [] 21

D -255 (с 10 CHCl3) IR (сm-1)

3447 1717 1642 1613 1H NMR (400 MHz CDCl3) δH 846 and 557 (2Н 2d J 35 Hz 33-Н 34-Н) 719 and

597 (2Н 2d J 161 Hz 28-Н 31-Н) 471 and 460 (2Н 2s 29-Н2) 316 (1Н dd J 50 112 Hz 3-Н) 247 (1Н

td J 112 54 Hz 19-Н) 168 (3Н s 30-Н3) 097 095 094 080 074 (15Н 5s 5СН3) 13C NMR (100 MHz

CDCl3) δC 18299 18259 15084 14969 12525 11005 10117 7897 5535 5042 5028 4991 4780

4282 4084 3896 3885 3879 3873 3719 3434 3354 2982 2798 2789 2740 2529 2077 1927

1827 1603 1599 1533 1469 Anal Calcd for C34H52O3 C 8026 H 1030 Found C 8041 H 1055



3β28-Dibenzoyloxy-20-(3acute-methyl-1H-pyrazol-5prime-yl)-30-norlup-20(29)-ene (18) Compound 14 (014 mmol)

was dissolved in 2 mL of ethanol and hydrazine hydrate (017 mmol) was added Then 2 ml of CH3COOH were

added under stirring The mixture was refluxed and monitored by TLC until the starting material completely

disappeared (15 h) The product was extracted with ethyl acetate The organic layer was separated washed

with H2O and dried over anhydrous MgSO4 The solvent was evaporated and the residue was subjected to CC

(eluent light petroleumminusethyl acetate 51) Yield 85 mp 1290 degС [] 21

D +160 (с 05 CHCl3) IR (сm-1)

3324 3206 1717 1H NMR (400 MHz CDCl3) δH 820 (1Н br s NН) 805-799 (4Н m Ph) 755-749 (2Н m

Ph) 743-737 (4Н m Ph) 612 (1H s 4prime-H) 539 and 511 (2Н 2s 29-Н2) 469 (1Н dd J 51 110 Hz 3-Н)

458 and 415 (2Н 2d J 111 Hz 28-Н2) 288 (1Н td J 112 55 Hz 19-Н) 228 (3Н s 6prime-Н3) 106 098 097

089 086 (15Н 5с 5СН3) 13C NMR (100 MHz CDCl3) δC 16686 16623 14963 14574 14399 13281

13260 13102 13051 12954 (2С) 12947 (2С) 12833 (2С) 12824 (2С) 10971 10262 8155 6325

55455055 5024 4680 4274 4095 3839 3818 3757 3710 3454 3418 3256 3010 2963 2809

2720 2706 2372 2097 1817 1673 1610 1608 1481 1207 Anal Calcd for C47H60N2O4 C 7873 H

843 N 391 Found C 7867 H 858 N 388

19β28-Epoxy-2-(3acute-methyl-1H-pyrazol-5prime-yl)-18αH-olean-1(2)en-3-one (19) Compound 16 (02 mmol) was

dissolved in 1 mL of ethanol with subsequent addition of hydrazine hydrate (022 mmol) Then 1 ml of

CH3COOH was added under stirring The mixture was refluxed and monitored by TLC until the starting material

completely disappeared (15 h) The product was extracted with ethyl acetate The organic layer was

separated washed with H2O and dried over anhydrous MgSO4 The solvent was evaporated and the residue


D +424 (с 05

CHCl3) IR (solution in CHCl3 сm-1) 3427 3206 1672 1H NMR (400 MHz CDCl3) δH 822 (1Н br s NH) 751

(1H s 1-Н) 623 (1H s 4acute-H) 378 and 345 (2H 2d J 79 Hz 28-H2) 354 (1H s 19-Н) 228 (3Н s 6acute-H3)

117 114 110 106 080 (15H 5s 5CH3) 094 (6H s 2CH3) Спектр 13C NMR (100 MHz CDCl3) δC 20482

15649 14712 14125 12455 10202 8787 7124 5262 4675 4540 4504 4162 4148 4107 3934

3673 3627 3443 3315 3270 2878 2866 2639 2631 2624 2453 2155 2150 1962 1919 1621

1333 1297 MS mz 5183 (M+) Anal Calcd for C34H50N2O2 C 7872 H 971 N 540 Found C 7896 H

964 N 557

3β-Hydroxy-28-[(1H-pyrazol-3prime-yl)methylylidene]lup-20(29)-ene (20) Compound 17 (058 mmol) was


CH3COOH were added under stirring The mixture was refluxed and monitored by TLC until the starting

material completely disappeared (15 h) The product was extracted with ethyl acetate The organic layer was



D -188 (с 06

CHCl3) IR (сm-1) 3209 1718 1642 1H NMR (400 MHz CDCl3) δH 749 and 633 (2Н 2d J 17 Hz 4acute-Н 5acute-Н)

648 and 644 (2Н 2d J 166 Hz 28-Н 31-Н) 579 (1Н s NH) 470 and 458 (2Н 2s 29-Н2) 317 (1Н dd J 51

110 Hz 3-Н) 246 (1Н td J = 110 48 Hz 19-Н) 168 (3Н s 30-Н3) 097 095 094 079 074 (15Н 5с

5СН3) 13C NMR (100 MHz CDCl3) δC 15024 14712 13688 13418 11866 10972 10188 7897 5535

5045 4978 4941 4795 4282 4087 3893 3885 3874 3844 3719 3432 3416 2998 2802 2784

2738 2528 2085 1932 1830 1605 1601 1540 1474 Anal Calcd for C34H52N2O C 8090 H 1038 N

555 Found C 8101 H 1022 N 534

3β28-Dibenzoyloxy-20-(3acute-methylisoxazol-5acute-yl)-30-norlup-20(29)-ene (21) Compound 14 (014 mmol) was

dissolved in 4 mL of ethanol with subsequent addition of hydrazine hydrate (014 mmol) and CH3COONa (014

mmol) The mixture was refluxed and monitored by TLC until the starting material completely disappeared



(15 h) The product was extracted with ethyl acetate The organic layer was separated washed with H2O and

dried over anhydrous MgSO4 The solvent was evaporated and the residue was subjected to CC (eluent light

petroleumminusethyl acetate 101) Yield 73 mp 690 degС [] 21

D +120 (с 05 CHCl3) IR (сm-1) 1716 1451 1H

NMR (400 MHz CDCl3) δH 806-800 (4Н m Ph) 756-749 (2Н m Ph) 744-738 (4Н m Ph) 612 (1H s 4prime-

H) 541 and 514 (2Н 2s 29-Н2) 469 (1Н dd J 52 109 Hz 3-Н) 458 and 416 (2Н 2d J 111 Hz 28-Н2) 287

(1Н td J 112 57 Hz 19-Н) 230 (3Н s 6prime-Н3) 107 099 097 090 087 (15Н 5s 5СН3) 13C NMR (100 MHz

CDCl3) δC 16692 16627 14917 14479 14410 13287 13263 13105 13050 12958 (2C) 12950 (2C)

12837 (2C) 12827 (2C) 10642 10291 8159 6320 5548 5067 5026 4686 4278 4100 3842 3821

3758 3714 3453 3421 3260 3010 2811 (2C) 2721 (2C) 2374 2100 1820 1676 1613 (2C) 1483

1197 Anal Calcd for C47H59NO5 C 7862 H 828 N 195 Found C 7881 H 841 N 211

19β28-Epoxy-2-(3acute-methylisoxazol-5acute-yl)-18αH-olean-1(2)en-3-one (22) Compound 16 (02 mmol) was

dissolved in 2 mL of ethanol with subsequent addition of hydroxylamine hydrochloride (022 mmol) and

CH3COONa (022 mmol) The mixture was refluxed and monitored by TLC until the starting material completely




D +367 (с 08 CHCl3) IR (сm-1) 1681

1626 1453 1H NMR (400 MHz CDCl3) δH 785 (1H s 1-Н) 661 (1H s 4acute-H) 380 and 349 (2H 2d J 78 Hz

28-H2) 359 (1H s 19-Н) 231 (3Н s 6acute-H3) 121 117 115 110 097 096 085 (21H 7s 7CH3) 13C NMR

(100 MHz CDCl3) δC 20156 16421 16035 15848 12372 10416 8787 7121 5250 4670 4529 4497

4163 4146 4104 3940 3671 3625 3444 3310 3270 2964 2875 2855 2637 2622 2452 2159

2146 1935 1923 1621 1329 1141 MS mz 51935 (M+) Anal Calcd for C34H49NO3 C 7857 H 950 N

269 Found C 7863 H 939 N 278

Acknowledgements

This research was financially supported by the State Contractual Order Nr АААА-А19-119031890083-9

Analytical and spectroscopic studies were performed at the Research of materials and substances collective

Center of PFRC UB RAS

Supplementary Material

Supplementary data related to this article can be found as the online version at httpdxdoiorg

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This paper is an open access article distributed under the terms of the Creative Commons Attribution (CC BY)

license (httpcreativecommonsorglicensesby40)


copyAUTHOR(S)

Introduction

The strategy for the design of hybrid molecules including those from natural compounds is based on the

methods of modern organic and medicinal chemistry and provides the preparation of chemical entities with

two (or more than two) structural domains with different biological functions1 In accord with the molecular

hybridization concept heterocyclic modification of triterpenic skeleton can provide new hybrid molecules with

high biological potential and bioavailability2-5 Concurrently β-dicarbonyl compounds have shown themselves

as useful building blocks for the construction of heterocycles with one two or more heteroatoms6-8 So 13-

diketones obtained from 3-oxo derivatives of allobetulin betulinic dihydrobetulonic 23-hydroxybetulinic

oleanolic maslinic and glycyrrhetinic acids were successfully used as convenient and promising objects in the

synthesis of NO-based five-membered heterocycles such as pyrazoles oxazoles and isoxazoles condensed

with triterpenic skeleton at the 23-position9-19 Herein we describe a convenient synthetic route for the

preparation of lupane and oleanane 13-diketones with use of the aldol condensation Further

heterocyclization of the synthesized triterpenic 13-diketones to derivatives with a 12-azole fragment

(pyrazole and isoxazole) in A or E cycles of triterpenoid has also been evinced as possible

Results and Discussion

Betulin 1 and its derivatives ndash 328-betulin dibenzoate 2 328-betulin diacetate 3 allobetulone 4 and betulinal

5 ndash were used as easily available starting compounds for the synthesis of new triterpenic 13-diketone

derivatives First via αβ-unsaturated aldehyde intermediates 6 7 920-23 compounds 2-4 were converted to β-

hydroxyketones 10-12 according to the antecedently described method2023 (Scheme 1)

The aldol reaction of compounds 10-12 with acetone was discontinued at first signs of the formation

(TLC) of a crotonrsquos by-product produced by the water elimination of their β-hydroxy ketone fragment In turn

the aldol condensation of betulinal 5 with acetone carried out at room temperature and using t-BuOKminust-BuOH

led to the formation of a new αβ-unsaturated methyl ketone 13 as a single product in an excellent 80 yield

The 1H NMR spectrum of αβ-unsaturated methyl ketone 13 showed CH3-33 protons of the methyl ketone

moiety recorded as a singlet at 227 ppm The E-configuration of the С-28 ndash С-31 double bond was confirmed

by a large coupling constant (165 Hz) between two olefinic protons at 616 and 707 ppm The signals of С-28

С-31 carbon atoms and carbonyl group were observed in 13C NMR spectrum of compound 13 at 13019

14962 and 19858 ppm respectively

The different location of aldehyde group in the structure of compounds 5-9 enabled the introduction of

a 13-diketone fragment at C-2 C-28 and C-30 positions of the triterpenic core According to TLC chromium

(VI) oxide in anhydrous pyridine normally used as an oxidation reagent was not suitable for β-hydroxy

ketones 10 and 11 because in both cases the reaction proceeded with the formation of a multicomponent

hard-to-separate product mixture Lupane 13-diketones 14 15 were obtained in 30 yields by treating

compounds 10 and 11 with PCC in anhydrous CH2Cl2 or with the Jones reagent in acetone (Scheme 2) 18αH-

Oleanane 13-diketone 16 was obtained by oxidation of β-hydroxy ketone 12 with the Jones reagent (other

oxidizing systems failed to lead to a good result)




betulin 1



































Conclusions



























D -240 (с 05




14962 13019 11006 7893 5533 5038 5006 4970 4785 4279 4082 3899 3884 3876 3872

3717 3429 3352 2979 2797 2785 2739 2713 2527 2076 1925 1825 1602 1590 1532 1469














MHz CDCl3) δC 19313 18530 16686 16622 15162 13286 13262 13100 13042 12953 (2С) 12947

(2С) 12835 (2С) 12825 (2С) 11864 9722 8151 6317 5546 5145 5021 4676 4271 4095 4092

3842 3817 3745 3711 3455 3418 3304 3011 2808 (2С) 2758 2715 2573 2371 2101 1816












17150 17094 15168 11864 9724 8091 6266 5542 5146 5022 4640 4266 4093 3844 3781

3738 3709 3439 3421 3301 2988 2794 (2С) 2757 2708 2577 2368 2124 2101 2097 1817











4673 4600 4481 4158 4148 4104 3956 3673 3627 3451 3292 3271 2877 2867 2658 2641


Found C 7822 H 985






D -255 (с 10 CHCl3) IR (сm-1)




CDCl3) δC 18299 18259 15084 14969 12525 11005 10117 7897 5535 5042 5028 4991 4780

4282 4084 3896 3885 3879 3873 3719 3434 3354 2982 2798 2789 2740 2529 2077 1927










D +160 (с 05 CHCl3) IR (сm-1)





13260 13102 13051 12954 (2С) 12947 (2С) 12833 (2С) 12824 (2С) 10971 10262 8155 6325

55455055 5024 4680 4274 4095 3839 3818 3757 3710 3454 3418 3256 3010 2963 2809


843 N 391 Found C 7867 H 858 N 388







D +424 (с 05




15649 14712 14125 12455 10202 8787 7124 5262 4675 4540 4504 4162 4148 4107 3934

3673 3627 3443 3315 3270 2878 2866 2639 2631 2624 2453 2155 2150 1962 1919 1621


964 N 557







D -188 (с 06





5045 4978 4941 4795 4282 4087 3893 3885 3874 3844 3719 3432 3416 2998 2802 2784


555 Found C 8101 H 1022 N 534









D +120 (с 05 CHCl3) IR (сm-1) 1716 1451 1H




CDCl3) δC 16692 16627 14917 14479 14410 13287 13263 13105 13050 12958 (2C) 12950 (2C)

12837 (2C) 12827 (2C) 10642 10291 8159 6320 5548 5067 5026 4686 4278 4100 3842 3821

3758 3714 3453 3421 3260 3010 2811 (2C) 2721 (2C) 2374 2100 1820 1676 1613 (2C) 1483








D +367 (с 08 CHCl3) IR (сm-1) 1681



(100 MHz CDCl3) δC 20156 16421 16035 15848 12372 10416 8787 7121 5250 4670 4529 4497

4163 4146 4104 3940 3671 3625 3444 3310 3270 2964 2875 2855 2637 2622 2452 2159


269 Found C 7863 H 939 N 278

Acknowledgements






References















httpsdoiorg101134S1070428015060019


httpsdoiorg101007s10593-020-02718-0


httpsdoiorg101016S0960-894X(03)00724-8




2009 19 6618











2014 84 223



25 728



424








httpdxdoiorg101080102860202011640774








httpsdoi101134s1070428019110083


Compd 2002 38 58

httpsdoiorg101023A1015733832373




copyAUTHOR(S)


betulin 1



































Conclusions



























D -240 (с 05




14962 13019 11006 7893 5533 5038 5006 4970 4785 4279 4082 3899 3884 3876 3872

3717 3429 3352 2979 2797 2785 2739 2713 2527 2076 1925 1825 1602 1590 1532 1469














MHz CDCl3) δC 19313 18530 16686 16622 15162 13286 13262 13100 13042 12953 (2С) 12947

(2С) 12835 (2С) 12825 (2С) 11864 9722 8151 6317 5546 5145 5021 4676 4271 4095 4092

3842 3817 3745 3711 3455 3418 3304 3011 2808 (2С) 2758 2715 2573 2371 2101 1816












17150 17094 15168 11864 9724 8091 6266 5542 5146 5022 4640 4266 4093 3844 3781

3738 3709 3439 3421 3301 2988 2794 (2С) 2757 2708 2577 2368 2124 2101 2097 1817











4673 4600 4481 4158 4148 4104 3956 3673 3627 3451 3292 3271 2877 2867 2658 2641


Found C 7822 H 985






D -255 (с 10 CHCl3) IR (сm-1)




CDCl3) δC 18299 18259 15084 14969 12525 11005 10117 7897 5535 5042 5028 4991 4780

4282 4084 3896 3885 3879 3873 3719 3434 3354 2982 2798 2789 2740 2529 2077 1927










D +160 (с 05 CHCl3) IR (сm-1)





13260 13102 13051 12954 (2С) 12947 (2С) 12833 (2С) 12824 (2С) 10971 10262 8155 6325

55455055 5024 4680 4274 4095 3839 3818 3757 3710 3454 3418 3256 3010 2963 2809


843 N 391 Found C 7867 H 858 N 388







D +424 (с 05




15649 14712 14125 12455 10202 8787 7124 5262 4675 4540 4504 4162 4148 4107 3934

3673 3627 3443 3315 3270 2878 2866 2639 2631 2624 2453 2155 2150 1962 1919 1621


964 N 557







D -188 (с 06





5045 4978 4941 4795 4282 4087 3893 3885 3874 3844 3719 3432 3416 2998 2802 2784


555 Found C 8101 H 1022 N 534









D +120 (с 05 CHCl3) IR (сm-1) 1716 1451 1H




CDCl3) δC 16692 16627 14917 14479 14410 13287 13263 13105 13050 12958 (2C) 12950 (2C)

12837 (2C) 12827 (2C) 10642 10291 8159 6320 5548 5067 5026 4686 4278 4100 3842 3821

3758 3714 3453 3421 3260 3010 2811 (2C) 2721 (2C) 2374 2100 1820 1676 1613 (2C) 1483








D +367 (с 08 CHCl3) IR (сm-1) 1681



(100 MHz CDCl3) δC 20156 16421 16035 15848 12372 10416 8787 7121 5250 4670 4529 4497

4163 4146 4104 3940 3671 3625 3444 3310 3270 2964 2875 2855 2637 2622 2452 2159


269 Found C 7863 H 939 N 278

Acknowledgements






References















httpsdoiorg101134S1070428015060019


httpsdoiorg101007s10593-020-02718-0


httpsdoiorg101016S0960-894X(03)00724-8




2009 19 6618











2014 84 223



25 728



424








httpdxdoiorg101080102860202011640774








httpsdoi101134s1070428019110083


Compd 2002 38 58

httpsdoiorg101023A1015733832373




copyAUTHOR(S)





















Conclusions



























D -240 (с 05




14962 13019 11006 7893 5533 5038 5006 4970 4785 4279 4082 3899 3884 3876 3872

3717 3429 3352 2979 2797 2785 2739 2713 2527 2076 1925 1825 1602 1590 1532 1469














MHz CDCl3) δC 19313 18530 16686 16622 15162 13286 13262 13100 13042 12953 (2С) 12947

(2С) 12835 (2С) 12825 (2С) 11864 9722 8151 6317 5546 5145 5021 4676 4271 4095 4092

3842 3817 3745 3711 3455 3418 3304 3011 2808 (2С) 2758 2715 2573 2371 2101 1816












17150 17094 15168 11864 9724 8091 6266 5542 5146 5022 4640 4266 4093 3844 3781

3738 3709 3439 3421 3301 2988 2794 (2С) 2757 2708 2577 2368 2124 2101 2097 1817











4673 4600 4481 4158 4148 4104 3956 3673 3627 3451 3292 3271 2877 2867 2658 2641


Found C 7822 H 985






D -255 (с 10 CHCl3) IR (сm-1)




CDCl3) δC 18299 18259 15084 14969 12525 11005 10117 7897 5535 5042 5028 4991 4780

4282 4084 3896 3885 3879 3873 3719 3434 3354 2982 2798 2789 2740 2529 2077 1927










D +160 (с 05 CHCl3) IR (сm-1)





13260 13102 13051 12954 (2С) 12947 (2С) 12833 (2С) 12824 (2С) 10971 10262 8155 6325

55455055 5024 4680 4274 4095 3839 3818 3757 3710 3454 3418 3256 3010 2963 2809


843 N 391 Found C 7867 H 858 N 388







D +424 (с 05




15649 14712 14125 12455 10202 8787 7124 5262 4675 4540 4504 4162 4148 4107 3934

3673 3627 3443 3315 3270 2878 2866 2639 2631 2624 2453 2155 2150 1962 1919 1621


964 N 557







D -188 (с 06





5045 4978 4941 4795 4282 4087 3893 3885 3874 3844 3719 3432 3416 2998 2802 2784


555 Found C 8101 H 1022 N 534









D +120 (с 05 CHCl3) IR (сm-1) 1716 1451 1H




CDCl3) δC 16692 16627 14917 14479 14410 13287 13263 13105 13050 12958 (2C) 12950 (2C)

12837 (2C) 12827 (2C) 10642 10291 8159 6320 5548 5067 5026 4686 4278 4100 3842 3821

3758 3714 3453 3421 3260 3010 2811 (2C) 2721 (2C) 2374 2100 1820 1676 1613 (2C) 1483








D +367 (с 08 CHCl3) IR (сm-1) 1681



(100 MHz CDCl3) δC 20156 16421 16035 15848 12372 10416 8787 7121 5250 4670 4529 4497

4163 4146 4104 3940 3671 3625 3444 3310 3270 2964 2875 2855 2637 2622 2452 2159


269 Found C 7863 H 939 N 278

Acknowledgements






References















httpsdoiorg101134S1070428015060019


httpsdoiorg101007s10593-020-02718-0


httpsdoiorg101016S0960-894X(03)00724-8




2009 19 6618











2014 84 223



25 728



424








httpdxdoiorg101080102860202011640774








httpsdoi101134s1070428019110083


Compd 2002 38 58

httpsdoiorg101023A1015733832373




copyAUTHOR(S)





Conclusions



























D -240 (с 05




14962 13019 11006 7893 5533 5038 5006 4970 4785 4279 4082 3899 3884 3876 3872

3717 3429 3352 2979 2797 2785 2739 2713 2527 2076 1925 1825 1602 1590 1532 1469














MHz CDCl3) δC 19313 18530 16686 16622 15162 13286 13262 13100 13042 12953 (2С) 12947

(2С) 12835 (2С) 12825 (2С) 11864 9722 8151 6317 5546 5145 5021 4676 4271 4095 4092

3842 3817 3745 3711 3455 3418 3304 3011 2808 (2С) 2758 2715 2573 2371 2101 1816












17150 17094 15168 11864 9724 8091 6266 5542 5146 5022 4640 4266 4093 3844 3781

3738 3709 3439 3421 3301 2988 2794 (2С) 2757 2708 2577 2368 2124 2101 2097 1817











4673 4600 4481 4158 4148 4104 3956 3673 3627 3451 3292 3271 2877 2867 2658 2641


Found C 7822 H 985






D -255 (с 10 CHCl3) IR (сm-1)




CDCl3) δC 18299 18259 15084 14969 12525 11005 10117 7897 5535 5042 5028 4991 4780

4282 4084 3896 3885 3879 3873 3719 3434 3354 2982 2798 2789 2740 2529 2077 1927










D +160 (с 05 CHCl3) IR (сm-1)





13260 13102 13051 12954 (2С) 12947 (2С) 12833 (2С) 12824 (2С) 10971 10262 8155 6325

55455055 5024 4680 4274 4095 3839 3818 3757 3710 3454 3418 3256 3010 2963 2809


843 N 391 Found C 7867 H 858 N 388







D +424 (с 05




15649 14712 14125 12455 10202 8787 7124 5262 4675 4540 4504 4162 4148 4107 3934

3673 3627 3443 3315 3270 2878 2866 2639 2631 2624 2453 2155 2150 1962 1919 1621


964 N 557







D -188 (с 06





5045 4978 4941 4795 4282 4087 3893 3885 3874 3844 3719 3432 3416 2998 2802 2784


555 Found C 8101 H 1022 N 534









D +120 (с 05 CHCl3) IR (сm-1) 1716 1451 1H




CDCl3) δC 16692 16627 14917 14479 14410 13287 13263 13105 13050 12958 (2C) 12950 (2C)

12837 (2C) 12827 (2C) 10642 10291 8159 6320 5548 5067 5026 4686 4278 4100 3842 3821

3758 3714 3453 3421 3260 3010 2811 (2C) 2721 (2C) 2374 2100 1820 1676 1613 (2C) 1483








D +367 (с 08 CHCl3) IR (сm-1) 1681



(100 MHz CDCl3) δC 20156 16421 16035 15848 12372 10416 8787 7121 5250 4670 4529 4497

4163 4146 4104 3940 3671 3625 3444 3310 3270 2964 2875 2855 2637 2622 2452 2159


269 Found C 7863 H 939 N 278

Acknowledgements






References















httpsdoiorg101134S1070428015060019


httpsdoiorg101007s10593-020-02718-0


httpsdoiorg101016S0960-894X(03)00724-8




2009 19 6618











2014 84 223



25 728



424








httpdxdoiorg101080102860202011640774








httpsdoi101134s1070428019110083


Compd 2002 38 58

httpsdoiorg101023A1015733832373




copyAUTHOR(S)

Conclusions



























D -240 (с 05




14962 13019 11006 7893 5533 5038 5006 4970 4785 4279 4082 3899 3884 3876 3872

3717 3429 3352 2979 2797 2785 2739 2713 2527 2076 1925 1825 1602 1590 1532 1469














MHz CDCl3) δC 19313 18530 16686 16622 15162 13286 13262 13100 13042 12953 (2С) 12947

(2С) 12835 (2С) 12825 (2С) 11864 9722 8151 6317 5546 5145 5021 4676 4271 4095 4092

3842 3817 3745 3711 3455 3418 3304 3011 2808 (2С) 2758 2715 2573 2371 2101 1816












17150 17094 15168 11864 9724 8091 6266 5542 5146 5022 4640 4266 4093 3844 3781

3738 3709 3439 3421 3301 2988 2794 (2С) 2757 2708 2577 2368 2124 2101 2097 1817











4673 4600 4481 4158 4148 4104 3956 3673 3627 3451 3292 3271 2877 2867 2658 2641


Found C 7822 H 985






D -255 (с 10 CHCl3) IR (сm-1)




CDCl3) δC 18299 18259 15084 14969 12525 11005 10117 7897 5535 5042 5028 4991 4780

4282 4084 3896 3885 3879 3873 3719 3434 3354 2982 2798 2789 2740 2529 2077 1927










D +160 (с 05 CHCl3) IR (сm-1)





13260 13102 13051 12954 (2С) 12947 (2С) 12833 (2С) 12824 (2С) 10971 10262 8155 6325

55455055 5024 4680 4274 4095 3839 3818 3757 3710 3454 3418 3256 3010 2963 2809


843 N 391 Found C 7867 H 858 N 388







D +424 (с 05




15649 14712 14125 12455 10202 8787 7124 5262 4675 4540 4504 4162 4148 4107 3934

3673 3627 3443 3315 3270 2878 2866 2639 2631 2624 2453 2155 2150 1962 1919 1621


964 N 557







D -188 (с 06





5045 4978 4941 4795 4282 4087 3893 3885 3874 3844 3719 3432 3416 2998 2802 2784


555 Found C 8101 H 1022 N 534









D +120 (с 05 CHCl3) IR (сm-1) 1716 1451 1H




CDCl3) δC 16692 16627 14917 14479 14410 13287 13263 13105 13050 12958 (2C) 12950 (2C)

12837 (2C) 12827 (2C) 10642 10291 8159 6320 5548 5067 5026 4686 4278 4100 3842 3821

3758 3714 3453 3421 3260 3010 2811 (2C) 2721 (2C) 2374 2100 1820 1676 1613 (2C) 1483








D +367 (с 08 CHCl3) IR (сm-1) 1681



(100 MHz CDCl3) δC 20156 16421 16035 15848 12372 10416 8787 7121 5250 4670 4529 4497

4163 4146 4104 3940 3671 3625 3444 3310 3270 2964 2875 2855 2637 2622 2452 2159


269 Found C 7863 H 939 N 278

Acknowledgements






References















httpsdoiorg101134S1070428015060019


httpsdoiorg101007s10593-020-02718-0


httpsdoiorg101016S0960-894X(03)00724-8




2009 19 6618











2014 84 223



25 728



424








httpdxdoiorg101080102860202011640774








httpsdoi101134s1070428019110083


Compd 2002 38 58

httpsdoiorg101023A1015733832373




copyAUTHOR(S)






MHz CDCl3) δC 19313 18530 16686 16622 15162 13286 13262 13100 13042 12953 (2С) 12947

(2С) 12835 (2С) 12825 (2С) 11864 9722 8151 6317 5546 5145 5021 4676 4271 4095 4092

3842 3817 3745 3711 3455 3418 3304 3011 2808 (2С) 2758 2715 2573 2371 2101 1816












17150 17094 15168 11864 9724 8091 6266 5542 5146 5022 4640 4266 4093 3844 3781

3738 3709 3439 3421 3301 2988 2794 (2С) 2757 2708 2577 2368 2124 2101 2097 1817











4673 4600 4481 4158 4148 4104 3956 3673 3627 3451 3292 3271 2877 2867 2658 2641


Found C 7822 H 985






D -255 (с 10 CHCl3) IR (сm-1)




CDCl3) δC 18299 18259 15084 14969 12525 11005 10117 7897 5535 5042 5028 4991 4780

4282 4084 3896 3885 3879 3873 3719 3434 3354 2982 2798 2789 2740 2529 2077 1927










D +160 (с 05 CHCl3) IR (сm-1)





13260 13102 13051 12954 (2С) 12947 (2С) 12833 (2С) 12824 (2С) 10971 10262 8155 6325

55455055 5024 4680 4274 4095 3839 3818 3757 3710 3454 3418 3256 3010 2963 2809


843 N 391 Found C 7867 H 858 N 388







D +424 (с 05




15649 14712 14125 12455 10202 8787 7124 5262 4675 4540 4504 4162 4148 4107 3934

3673 3627 3443 3315 3270 2878 2866 2639 2631 2624 2453 2155 2150 1962 1919 1621


964 N 557







D -188 (с 06





5045 4978 4941 4795 4282 4087 3893 3885 3874 3844 3719 3432 3416 2998 2802 2784


555 Found C 8101 H 1022 N 534









D +120 (с 05 CHCl3) IR (сm-1) 1716 1451 1H




CDCl3) δC 16692 16627 14917 14479 14410 13287 13263 13105 13050 12958 (2C) 12950 (2C)

12837 (2C) 12827 (2C) 10642 10291 8159 6320 5548 5067 5026 4686 4278 4100 3842 3821

3758 3714 3453 3421 3260 3010 2811 (2C) 2721 (2C) 2374 2100 1820 1676 1613 (2C) 1483








D +367 (с 08 CHCl3) IR (сm-1) 1681



(100 MHz CDCl3) δC 20156 16421 16035 15848 12372 10416 8787 7121 5250 4670 4529 4497

4163 4146 4104 3940 3671 3625 3444 3310 3270 2964 2875 2855 2637 2622 2452 2159


269 Found C 7863 H 939 N 278

Acknowledgements






References















httpsdoiorg101134S1070428015060019


httpsdoiorg101007s10593-020-02718-0


httpsdoiorg101016S0960-894X(03)00724-8




2009 19 6618











2014 84 223



25 728



424








httpdxdoiorg101080102860202011640774








httpsdoi101134s1070428019110083


Compd 2002 38 58

httpsdoiorg101023A1015733832373




copyAUTHOR(S)







D +160 (с 05 CHCl3) IR (сm-1)





13260 13102 13051 12954 (2С) 12947 (2С) 12833 (2С) 12824 (2С) 10971 10262 8155 6325

55455055 5024 4680 4274 4095 3839 3818 3757 3710 3454 3418 3256 3010 2963 2809


843 N 391 Found C 7867 H 858 N 388







D +424 (с 05




15649 14712 14125 12455 10202 8787 7124 5262 4675 4540 4504 4162 4148 4107 3934

3673 3627 3443 3315 3270 2878 2866 2639 2631 2624 2453 2155 2150 1962 1919 1621


964 N 557







D -188 (с 06





5045 4978 4941 4795 4282 4087 3893 3885 3874 3844 3719 3432 3416 2998 2802 2784


555 Found C 8101 H 1022 N 534









D +120 (с 05 CHCl3) IR (сm-1) 1716 1451 1H




CDCl3) δC 16692 16627 14917 14479 14410 13287 13263 13105 13050 12958 (2C) 12950 (2C)

12837 (2C) 12827 (2C) 10642 10291 8159 6320 5548 5067 5026 4686 4278 4100 3842 3821

3758 3714 3453 3421 3260 3010 2811 (2C) 2721 (2C) 2374 2100 1820 1676 1613 (2C) 1483








D +367 (с 08 CHCl3) IR (сm-1) 1681



(100 MHz CDCl3) δC 20156 16421 16035 15848 12372 10416 8787 7121 5250 4670 4529 4497

4163 4146 4104 3940 3671 3625 3444 3310 3270 2964 2875 2855 2637 2622 2452 2159


269 Found C 7863 H 939 N 278

Acknowledgements






References















httpsdoiorg101134S1070428015060019


httpsdoiorg101007s10593-020-02718-0


httpsdoiorg101016S0960-894X(03)00724-8




2009 19 6618











2014 84 223



25 728



424








httpdxdoiorg101080102860202011640774








httpsdoi101134s1070428019110083


Compd 2002 38 58

httpsdoiorg101023A1015733832373




copyAUTHOR(S)




D +120 (с 05 CHCl3) IR (сm-1) 1716 1451 1H




CDCl3) δC 16692 16627 14917 14479 14410 13287 13263 13105 13050 12958 (2C) 12950 (2C)

12837 (2C) 12827 (2C) 10642 10291 8159 6320 5548 5067 5026 4686 4278 4100 3842 3821

3758 3714 3453 3421 3260 3010 2811 (2C) 2721 (2C) 2374 2100 1820 1676 1613 (2C) 1483








D +367 (с 08 CHCl3) IR (сm-1) 1681



(100 MHz CDCl3) δC 20156 16421 16035 15848 12372 10416 8787 7121 5250 4670 4529 4497

4163 4146 4104 3940 3671 3625 3444 3310 3270 2964 2875 2855 2637 2622 2452 2159


269 Found C 7863 H 939 N 278

Acknowledgements






References















httpsdoiorg101134S1070428015060019


httpsdoiorg101007s10593-020-02718-0


httpsdoiorg101016S0960-894X(03)00724-8




2009 19 6618











2014 84 223



25 728



424








httpdxdoiorg101080102860202011640774








httpsdoi101134s1070428019110083


Compd 2002 38 58

httpsdoiorg101023A1015733832373




copyAUTHOR(S)








httpsdoiorg101134S1070428015060019


httpsdoiorg101007s10593-020-02718-0


httpsdoiorg101016S0960-894X(03)00724-8




2009 19 6618











2014 84 223



25 728



424








httpdxdoiorg101080102860202011640774








httpsdoi101134s1070428019110083


Compd 2002 38 58

httpsdoiorg101023A1015733832373




copyAUTHOR(S)



httpsdoi101134s1070428019110083


Compd 2002 38 58

httpsdoiorg101023A1015733832373



Synthesis and heterocyclization of triterpenic 1,3-diketones

Documents

Transcript of Synthesis and heterocyclization of triterpenic 1,3-diketones