S1

Electronic Supplementary Information

Modeling of synthetic phosphono and carba analogues of N-acetyl-α-D-mannosamine 1-phosphate, the repeating unit of a capsular polysaccharidefrom Neisseria meningitidis serovar A†

Lucio Toma,*a Laura Legnani,a Anna Rencurosi,b,c Laura Poletti,b Luigi Lay*b and Giovanni Russo b

a Dipartimento di Chimica Organica, Università di Pavia, Via Taramelli 10, 27100 Pavia, Italy

b Dipartimento di Chimica Organica e Industriale and CISI, Università di Milano, Via Venezian 21,

20133 Milano, Italy

c Present address: NiKem Research Srl, Via Zambeletti, 25, 20021 Baranzate (MI), Italy

S2

B3LYP/6-311+G(d,p) (for C, H, O, N atoms) and 6-311+G(2df,p) level (for P atom) energies (recalculated in water using the continuum solvent model C-PCM), zero- point energy corrections and cartesian coordinates of conformers of compounds 1-3 1A Ewater = -1427.008492 zero-point correction = 0.288619 C 1.38898100 0.53570000 1.36333900 C 1.35120700 -0.64433500 0.37428500 C 0.03850400 -0.56802500 -0.43403200 C -0.14971100 1.80083800 -0.16177500 C 1.12562900 1.88941300 0.68306600 H 0.03503000 -1.29219400 -1.25251900 H 1.41441900 -1.58289900 0.92418400 H 0.56980200 0.36527800 2.07588300 H -0.99572700 1.58681800 0.50207100 H 1.98322800 2.16161600 0.05984400 O 0.00232300 0.70764700 -1.08105900 O -1.04525500 -0.76316300 0.41572000 P -2.59372900 -0.76291900 -0.27543700 O -2.57187500 -1.72648100 -1.40491500 O -3.36987100 -1.37555200 1.01368900 C -3.22498400 -2.76194600 1.30425600 H -2.23806700 -2.96754800 1.73412400 H -3.99511600 -3.01876500 2.03617900 H -3.35329400 -3.36493200 0.40167900 O -3.02900800 0.65771300 -0.40170400 N 2.46647700 -0.62133700 -0.56254000 H 2.41787700 0.06458500 -1.30046700 C 3.46322900 -1.54808900 -0.59384600 O 3.55161800 -2.48590300 0.18560100 C 4.50038800 -1.33824000 -1.68969900 H 4.28099900 -0.49440300 -2.34768100 H 5.47231700 -1.17713100 -1.21775200 H 4.56770100 -2.25051800 -2.28578800 O 1.06634400 2.91880300 1.68782500 H 0.21393400 2.84470200 2.13464500 O 2.63448700 0.54942200 2.05432400 H 2.66197000 1.38376500 2.53812100 C -0.50878900 3.03221800 -0.97745500 H -0.35720600 3.92287800 -0.35364000 H 0.18159800 3.10261700 -1.83171600 O -1.84480500 3.01227200 -1.44033000 H -2.27726100 2.16600100 -1.18987100

1B Ewater = -1427.007975 zero-point correction = 0.288246 C -0.51812900 2.90361900 -1.32561200 C -0.15072800 1.82009500 -0.32490000 C 1.17833900 1.99926400 0.41758400 C 1.46564600 0.75944000 1.28051600 C 1.33505300 -0.55766500 0.49303600 C -0.03878800 -0.56536100 -0.21445300 O 1.20223800 3.17309000 1.24943600 O 2.76050600 0.84225700 1.86928200 H -0.96025800 1.75894400 0.41239500 H 1.99758900 2.14920800 -0.29290900 H 0.69912200 0.72181300 2.06650400 H 1.42388600 -1.40099300 1.17691200 H -0.11355300 -1.40750500 -0.90807700 H 0.38802900 3.18278800 1.76798700 H 2.83451600 1.73341400 2.23136600 H 0.14706200 2.81179900 -2.19885000 H -0.33485800 3.88479900 -0.86997800 N 2.37460900 -0.71103700 -0.51531300 H 2.30316500 -0.11813600 -1.32786100 C 3.33225700 -1.67822100 -0.49349000 O 3.43971900 -2.51695300 0.38964900 C 4.30204200 -1.64691700 -1.66812700 H 4.03001100 -0.92800700 -2.44439300 H 5.29546300 -1.39701000 -1.28769000 H 4.35488600 -2.64617900 -2.10406400 O -1.86970400 2.83031600 -1.73067400 H -2.27437300 2.00017600 -1.39317700 O -1.04036200 -0.60949900 0.75169700 P -2.68062900 -0.63536800 0.34660800 O -2.97766600 0.57737900 -0.46524800 O -3.37134400 -0.97399700 1.61135000 O -2.69819300 -1.90663900 -0.68446000 C -2.71614000 -3.22464300 -0.14316100 H -2.96258100 -3.90441800 -0.96307500 H -1.73637500 -3.49987200 0.26625500 H -3.46144500 -3.30792300 0.65106200 O -0.09274800 0.58620000 -1.05386900

S3

1C Ewater = -1427.007260 zero-point correction = 0.288508 C 1.31756300 0.67216300 1.31737800 C 1.42560400 -0.58627700 0.43648900 C 0.14411700 -0.70874700 -0.41572200 C -0.27790600 1.64743800 -0.34794500 C 0.95954400 1.92987300 0.50994400 H 0.24907900 -1.48981600 -1.17246000 H 1.55419500 -1.46405600 1.06912900 H 0.48963700 0.48880200 2.01717400 H -1.11573300 1.40652900 0.31759800 H 1.80759500 2.21992400 -0.11786500 O 0.00365200 0.50263400 -1.16753100 O -0.94956100 -0.95423700 0.40700400 P -2.45087200 -1.18035800 -0.34776800 O -2.28604700 -2.18988600 -1.41417900 O -3.20660500 -1.86473900 0.91661600 C -3.62864600 -1.06063400 2.01050400 H -4.09432500 -0.13665400 1.65817000 H -4.35282000 -1.64708200 2.58214800 H -2.78123000 -0.81308400 2.66153400 O -3.01921700 0.18870600 -0.57346400 N 2.56769900 -0.53517300 -0.46665200 H 2.47200900 0.05738800 -1.27726900 C 3.66340700 -1.33791000 -0.36812000 O 3.82710200 -2.16892800 0.51293200 C 4.71123100 -1.12796200 -1.45404100 H 4.91688800 -2.08856400 -1.93033700 H 4.41567700 -0.40418900 -2.21692400 H 5.63482400 -0.78724400 -0.98035100 O 0.78047400 3.03744000 1.41244500 H -0.07364300 2.92731000 1.84812600 O 2.52813900 0.86115800 2.04293400 H 2.46805500 1.73806600 2.44091900 C -0.73744100 2.76411700 -1.27207600 H -0.65991200 3.72000100 -0.73886500 H -0.05504800 2.80697800 -2.13476500 O -2.07095600 2.59461500 -1.71180100 H -2.40674300 1.71081600 -1.44099200 1D Ewater = -1427.006258 zero-point correction =0.288146 C 1.24694800 0.62604700 1.30927400 C 1.31155300 -0.66494000 0.47722800

C 0.00860200 -0.78827200 -0.34225600 C -0.27155600 1.59344800 -0.44961400 C 0.95933700 1.84877900 0.43732500 H 0.05051600 -1.61423600 -1.05280400 H 1.41519100 -1.51998400 1.14406100 H 0.40994800 0.51312800 2.00732000 H -1.16149400 1.52006400 0.18317700 H 1.83133700 2.03386900 -0.20932300 O -0.08729900 0.38762000 -1.18430500 O -1.06193200 -0.91769100 0.52034100 P -2.50068600 -1.65113300 -0.00782300 O -3.11514500 -2.21428900 1.21872400 O -3.34305400 -0.30874400 -0.45680400 C -4.04987800 0.41646900 0.53976900 H -3.36537700 0.97060200 1.19565200 H -4.69741000 1.13075900 0.02177900 H -4.65091700 -0.25265000 1.16015700 O -2.17713700 -2.39968200 -1.24624800 N 2.44464500 -0.69219400 -0.44095500 H 2.35207500 -0.14260900 -1.28099000 C 3.51761000 -1.52168000 -0.32353200 O 3.68014100 -2.31257000 0.59341500 C 4.54770300 -1.39728800 -1.44103400 H 4.26008800 -0.69877100 -2.23046600 H 5.49304900 -1.06844700 -1.00317200 H 4.70913300 -2.38508800 -1.87722600 O 0.78818100 2.95645400 1.32868600 H 0.40149800 3.67970900 0.81647100 O 2.46471600 0.80143700 2.03111900 H 2.38842200 1.64957500 2.48327500 C -0.49620400 2.65925400 -1.51441500 H 0.35701200 2.66892000 -2.20411400 H -1.40269700 2.40943000 -2.07273700 O -0.62824900 3.94185000 -0.86736600 H -0.79907700 4.61209100 -1.53399900 1E Ewater = -1427.005912 zero-point correction = 0.288126 C 1.41907900 0.54951200 1.30594800 C 1.25761700 -0.72779700 0.46675200 C -0.14031300 -0.71128000 -0.18688600 C -0.19444600 1.69113700 -0.25623500 C 1.15338400 1.80718100 0.47751600 H -0.26471000 -1.53575700 -0.89102500 H 1.35301800 -1.60002100 1.11227500 H 0.66277800 0.50767800 2.09721400 H -1.00810500 1.69197500 0.47606100 H 1.95622600 1.91305300 -0.26933700 O -0.21948300 0.48190500 -1.01666500 O -1.10767200 -0.72709900 0.79209500

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P -2.64239600 -1.38660200 0.49432000 O -3.22439300 -1.57925700 1.83712000 O -3.39534600 -0.08931800 -0.18914800 C -3.55153000 -0.01929000 -1.59986300 H -3.88395700 -0.97646700 -2.00866800 H -4.30436600 0.75030100 -1.80009200 H -2.61215400 0.25895400 -2.09228800 O -2.46481900 -2.43561800 -0.54934500 N 2.26569600 -0.85285700 -0.57953400 H 2.14225800 -0.27116300 -1.39334400 C 3.25375700 -1.78969500 -0.59421300 O 3.43453100 -2.61329500 0.28954500 C 4.16133300 -1.74414300 -1.81865300 H 3.84418200 -1.02408400 -2.57689300 H 5.17171400 -1.48993000 -1.48952600 H 4.19699500 -2.74096800 -2.26221900 O 1.20474600 2.91211800 1.38540200 H 0.83259900 3.67822400 0.92785900 O 2.72551100 0.59451900 1.87638200 H 2.78346600 1.43439400 2.34632500 C -0.42710300 2.79435800 -1.28202700 H 0.33238200 2.72210000 -2.07080600 H -1.41672400 2.65924600 -1.72789300 O -0.33748600 4.07148000 -0.61984000 H -0.52492200 4.76812400 -1.25412000 1F Ewater = -1427.005977 zero-point correction = 0.288482 C 0.90378400 2.53949400 1.45424500 C 0.32224400 1.62418400 0.38904600 C -1.04845800 2.01919100 -0.17019400 C -1.53725800 0.94390600 -1.15407500 C -1.46410700 -0.47679200 -0.56561800 C -0.04370700 -0.70655800 -0.00487600 O -1.03705300 3.29736500 -0.83157400 O -2.86668800 1.21959500 -1.58465700 H 1.04016500 1.58248900 -0.43822800 H -1.77590200 2.13566100 0.63942900 H -0.85577100 0.95390700 -2.01618700 H -1.69213300 -1.20586000 -1.34229200 H -0.00309700 -1.63925100 0.56304500 H -0.28777900 3.30718300 -1.44020600 H -2.88639400 2.15657900 -1.81355000 H 0.30227900 2.45304600 2.37095900 H 0.82226300 3.57682600 1.10133100 N -2.42217500 -0.68287100 0.51213600 H -2.21866700 -0.22944300 1.38943600 C -3.48927200 -1.52630000 0.44470500 O -3.77197400 -2.19710100 -0.53684900 C -4.34420800 -1.58091000 1.70480900

H -3.93346200 -1.01094000 2.54145900 H -5.33610200 -1.19080200 1.46444300 H -4.46116900 -2.62461900 2.00237900 O 2.25134800 2.23318200 1.75406600 H 2.58349500 1.55704500 1.11987400 O 0.86769900 -0.71665800 -1.05398900 P 2.52285200 -0.89362100 -0.80548800 O 3.03586100 0.35839500 -0.15736900 O 3.05462600 -1.40558000 -2.08250000 O 2.48119900 -2.08144600 0.32329000 C 3.08216700 -1.88069200 1.59982800 H 2.87947600 -2.78159400 2.18566200 H 4.16488600 -1.74715400 1.51151000 H 2.66364000 -1.00796900 2.10638900 O 0.21243300 0.31301900 0.96516900 1G Ewater = -1427.004906 zero-point correction = 0.287929 C 1.38386500 0.59774500 1.30020300 C 1.36112300 -0.69066300 0.46076600 C 0.00840500 -0.76971700 -0.27860200 C -0.22598100 1.61285100 -0.34671000 C 1.06774600 1.83332400 0.45564800 H -0.02414100 -1.59809500 -0.98714800 H 1.48067900 -1.55242800 1.11615400 H 0.59370500 0.50166700 2.05285400 H -1.07784300 1.54386400 0.33643000 H 1.89801700 2.00224000 -0.24847100 O -0.10754600 0.40882400 -1.10465900 O -1.00777900 -0.86482300 0.65717700 P -2.50418700 -1.48744600 0.23159000 O -3.15185200 -1.95036400 1.48229700 O -3.17005000 -0.03377600 -0.20770100 C -4.57191300 -0.02788000 -0.42184100 H -5.10554600 -0.38344600 0.46631200 H -4.86819900 1.00413300 -0.63337500 H -4.84614500 -0.65837300 -1.27723400 O -2.32470600 -2.33685400 -0.97753600 N 2.43571900 -0.74524400 -0.52326800 H 2.32565500 -0.16420300 -1.33953400 C 3.48012800 -1.61708400 -0.48177400 O 3.65779800 -2.43728900 0.40635900 C 4.45769900 -1.50062800 -1.64607300 H 4.14434400 -0.79115000 -2.41568000 H 5.42788300 -1.18948300 -1.25139200 H 4.58248400 -2.48734100 -2.09612800 O 0.98784000 2.93820900 1.36270000 H 0.57484000 3.67121300 0.88612900 O 2.65245700 0.73802300 1.93775000 H 2.62660000 1.58312200 2.40116700

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C -0.49872300 2.69077700 -1.38730600 H 0.29992000 2.68201100 -2.13983200 H -1.45204800 2.46919400 -1.87486000 O -0.54541800 3.97231100 -0.72654600 H -0.76747700 4.64903600 -1.37096600 2A Ewater = -1391.054422 zero-point correction = 0.311469 C -0.26950300 2.92708600 -1.12745200 C 0.04332000 1.76330300 -0.19360400 C 1.38746500 1.85571700 0.54020600 C 1.64228500 0.56772200 1.33597900 C 1.46660600 -0.69991800 0.47832700 C 0.09100500 -0.65046900 -0.23164600 O 1.47471800 2.98574500 1.42837700 O 2.93683700 0.58276900 1.92818700 H -0.76928700 1.70970000 0.54433700 H 2.19979000 2.00527300 -0.17790200 H 0.88347700 0.52196900 2.13155200 H 1.55388400 -1.57911500 1.11837600 H 0.07309200 -1.42541600 -0.99967700 H 0.64215000 3.04956300 1.91199300 H 3.04911200 1.46537500 2.30210600 H 0.32158200 2.78385400 -2.04663200 H 0.06930000 3.85920600 -0.65807200 N 2.51269700 -0.81686600 -0.53258900 H 2.40989800 -0.23095700 -1.34748000 C 3.46468100 -1.78857600 -0.54043000 O 3.58539400 -2.63633000 0.33364100 C 4.40761600 -1.75599100 -1.73630700 H 4.15575300 -0.99095500 -2.47416100 H 5.42161100 -1.57710000 -1.37121100 H 4.39580100 -2.73639000 -2.21667400 O -1.64094800 3.05122200 -1.42753900 H -2.12370300 2.22806400 -1.17114900 P -2.73997300 -0.59815900 -0.22176700 O -2.81573300 -1.55774600 -1.36156400 O -2.94269200 0.88085700 -0.36611800 O -3.80053300 -1.06121600 0.96093500 C -4.18303200 -2.42417300 1.06475900 H -5.15086200 -2.45875900 1.57428100 H -4.26643500 -2.88289500 0.07661700 H -3.45844100 -2.99767000 1.66105200 O 0.05242800 0.57427500 -0.98639600 C -1.12851700 -0.87086300 0.66834000 H -1.12359500 -0.24159600 1.56233500 H -1.09971200 -1.91133500 1.00973300

2B Ewater = -1391.053710 zero-point correction = 0.311422 C 0.42676400 2.74036500 1.45050200 C 0.03725000 1.75712900 0.35364600 C -1.36681400 1.96341800 -0.23038100 C -1.70999200 0.82527300 -1.20176700 C -1.46106700 -0.56717900 -0.59244200 C -0.01995700 -0.62456200 -0.02432200 O -1.52228500 3.22537300 -0.90568300 O -3.05735900 0.92834800 -1.65026700 H 0.78238800 1.84493400 -0.44942200 H -2.10862400 1.98848100 0.57414300 H -1.03545200 0.92074300 -2.06555200 H -1.61874700 -1.32662700 -1.35952300 H 0.05868800 -1.51888100 0.59651600 H -0.74002900 3.36905000 -1.45212800 H -3.19689700 1.85847900 -1.86634600 H -0.14296700 2.47367400 2.35584300 H 0.11133700 3.74754700 1.14812600 N -2.40303200 -0.86161100 0.48293200 H -2.23137800 -0.39933200 1.36305100 C -3.34360000 -1.84280000 0.43197400 O -3.53881800 -2.55530700 -0.54353500 C -4.17214800 -2.00653400 1.69981400 H -3.86908800 -1.34276300 2.51274500 H -5.21876500 -1.81230100 1.45455400 H -4.09711900 -3.04300900 2.03515100 O 1.80846600 2.75680100 1.72287800 H 2.25592500 2.00731100 1.25919400 P 2.84148300 -0.50554200 -0.46278100 O 2.98262500 0.85150800 0.15707000 O 3.74019300 -0.97821400 -1.55605300 O 2.86849600 -1.59291200 0.78164000 C 3.22745100 -2.94357000 0.52869400 H 3.59259300 -3.36942500 1.46812800 H 2.35957200 -3.53159800 0.19671200 H 4.00536900 -3.00509000 -0.23579900 O 0.09586300 0.44879900 0.92313100 C 1.09408600 -0.68856100 -1.07675700 H 0.97929200 0.06077500 -1.86525800 H 1.02360400 -1.66061200 -1.57617400 2C Ewater = -1391.052891 zero-point correction = 0.311551 C 0.81975200 2.46484100 1.45087500 C 0.25621800 1.58600000 0.34137700

S6

C -1.14329800 1.98687300 -0.14402300 C -1.67417100 0.95525600 -1.14934700 C -1.55631800 -0.48984100 -0.62896000 C -0.10297200 -0.74562100 -0.15735700 O -1.18472200 3.29609100 -0.74152000 O -3.02400900 1.23856600 -1.50164400 H 0.96002300 1.62521700 -0.50135400 H -1.83074400 2.05089000 0.70529800 H -1.04562800 1.02412800 -2.04954200 H -1.84442700 -1.18064800 -1.42250500 H -0.09299600 -1.68125800 0.40413400 H -0.43445700 3.37268500 -1.34359000 H -3.06602200 2.18968600 -1.65936800 H 0.21396200 2.30960600 2.35680000 H 0.69624300 3.51555400 1.15108800 N -2.46383800 -0.73593300 0.48724300 H -2.18578100 -0.35464000 1.37871900 C -3.53010600 -1.57955400 0.43913700 O -3.87402000 -2.19251900 -0.56208000 C -4.30029600 -1.71812800 1.74626700 H -3.85669900 -1.16786000 2.57920900 H -5.31887800 -1.35741600 1.58570000 H -4.36064000 -2.77693900 2.00592000 O 2.17202600 2.19794700 1.74342700 H 2.54098200 1.56161700 1.08013400 P 2.72914000 -0.85035400 -0.77373900 O 3.06226500 0.49400200 -0.17441700 O 3.49982000 -1.39736400 -1.92099400 O 2.69523800 -1.96754800 0.44176900 C 3.05528500 -1.60640100 1.77133000 H 2.92603700 -2.50186100 2.38676400 H 4.09955800 -1.28374700 1.82756000 H 2.42247100 -0.80245300 2.15587900 O 0.19151300 0.24921500 0.84247800 C 0.93841200 -0.86602800 -1.27540300 H 0.83857200 -0.08892200 -2.03871000 H 0.76826700 -1.81829900 -1.78628100 2D Ewater = -1391.051740 zero-point correction = 0.311881 C -2.24186700 -2.26711400 -0.76364100 C -2.34000100 -1.38821400 0.49689900 C -3.00153300 -0.02025400 0.28386800 C -2.03945100 1.01413100 -0.32652700 C -0.65908300 0.99940600 0.37040000 C -0.10872900 -0.43653600 0.45586600 O -3.52637900 0.46734700 1.52548300 O -1.90744900 0.72227500 -1.72156600 H -2.96356900 -1.93179200 1.21803900 H -3.86205100 -0.13149000 -0.37858400

H -2.48394900 2.00482900 -0.19168700 H -0.79463600 1.37804700 1.39124100 H -0.00071000 -0.84404200 -0.55431600 H -2.80792600 0.46101400 2.16873600 H -1.12861700 1.20796900 -2.02652200 H -1.53581600 -3.08126100 -0.55936500 H -1.89465700 -1.70382300 -1.62659900 N 0.27873700 1.87148900 -0.33042600 H 1.16552600 1.42639900 -0.66151000 C 0.28860700 3.21388400 -0.10220800 O -0.57298000 3.80151500 0.54922600 C 1.44756800 3.95727800 -0.74779300 H 2.23548700 3.28511200 -1.09055200 H 1.06763000 4.53428800 -1.59627500 H 1.85180500 4.66558500 -0.02218000 O -3.52783000 -2.78185400 -1.13351100 H -3.86053200 -3.31004100 -0.40044200 P 2.72946300 -0.55411600 0.10960600 O 3.93970400 -0.67764400 0.96929700 O 2.55929100 0.54645600 -0.90513900 O 2.51249900 -1.94874400 -0.75200700 C 2.96378300 -3.17967800 -0.20494200 H 3.04830700 -3.89386800 -1.02913200 H 3.93396300 -3.05717500 0.28269100 H 2.24757500 -3.57742900 0.52779100 O -1.08720400 -1.23857700 1.16935600 C 1.22484500 -0.56721300 1.19340300 H 1.34368300 0.21846800 1.94617600 H 1.22332100 -1.51981000 1.73033200 3A Ewater = -1391.089540 zero-point correction = 0.312124 C 1.17344900 0.72234600 1.22803900 C 1.37109500 -0.58666100 0.45193900 C 0.12222800 -0.87253300 -0.41645400 C -0.41527600 1.62189200 -0.52989200 C 0.82504500 1.91274900 0.32718600 H 0.32026800 -1.74641900 -1.04283000 H 1.49409800 -1.40593200 1.15969000 H 0.32188900 0.56380200 1.89803900 H -1.27077600 1.47514400 0.13550000 H 1.67915400 2.12154500 -0.34274500 O -0.93701500 -1.15993300 0.48509400 P -2.39744600 -1.74462000 -0.08847500 O -2.96347100 -2.58137600 0.99794800 O -3.25415700 -0.32708300 -0.16254800 C -3.83049700 0.17369700 1.03522200 H -3.06291200 0.56013700 1.71919400 H -4.50030200 0.99377500 0.75742300 H -4.39099800 -0.60723300 1.55535300

S7

O -2.19340900 -2.16958300 -1.49870500 N 2.59010500 -0.55295000 -0.35600900 H 2.79741500 0.29384200 -0.85929200 C 3.59391200 -1.46985600 -0.25965700 O 3.53244300 -2.48800400 0.41210500 C 4.84136600 -1.14447800 -1.07412500 H 4.73127800 -0.27004900 -1.72046800 H 5.66902400 -0.97080500 -0.38208900 H 5.09462800 -2.01239700 -1.68556800 O 0.67391500 3.03398300 1.21106300 H 0.13760700 3.69603000 0.75238600 O 2.34795500 1.01018700 1.98991100 H 2.19308200 1.87166300 2.39568000 C -0.75566100 2.75095900 -1.49429100 H 0.07675900 2.91816400 -2.19289700 H -1.64473500 2.47469300 -2.07060700 O -1.01277400 3.97054400 -0.75731800 H -1.22885100 4.67319800 -1.37651100 C -0.20197300 0.32198900 -1.32699800 H -1.09545800 0.07009200 -1.90071900 H 0.61976700 0.45018300 -2.04655300 3B Ewater = -1391.089366 zero-point correction = 0.312476 C -1.50071600 0.00426000 1.33164100 C -0.68472600 1.07714400 0.60367100 C 0.37082100 0.39716300 -0.30452900 C -1.04443200 -1.70869100 -0.47290200 C -2.11747200 -1.03982900 0.39446000 H 0.87680300 1.16921000 -0.89129800 H -0.14513300 1.67511700 1.34267500 H -0.81798400 -0.51752600 2.00749600 H -0.33279200 -2.22517500 0.17893900 H -2.84365100 -0.54124100 -0.27007400 O 1.28988900 -0.21412800 0.59288100 P 2.76204100 -0.81875700 0.07411400 O 2.53606700 -1.67398600 -1.12369500 O 3.46097300 0.56152100 -0.48698900 C 3.93200900 1.51529300 0.45607900 H 4.53662300 1.03229200 1.22891800 H 4.53865800 2.24150200 -0.09297500 H 3.09951900 2.04343700 0.93637800 O 3.44174000 -1.27016300 1.31404200 N -1.59860000 1.95577500 -0.13709800 H -2.57997200 1.78979200 0.03139600 C -1.25694700 3.20834800 -0.55016000 O -0.11718200 3.64903500 -0.51945300 C -2.41132500 4.05241600 -1.08079300 H -3.34940700 3.50107400 -1.17804700 H -2.56358600 4.89820100 -0.40537800

H -2.12833900 4.45428900 -2.05540400 O -2.84054500 -1.93788600 1.25271800 H -2.92229900 -2.78232100 0.78686900 O -2.54301800 0.64546700 2.08579900 H -3.08369000 -0.07128400 2.44054100 C -1.61399300 -2.72367800 -1.45467500 H -2.31246000 -2.23283600 -2.14733500 H -0.79311400 -3.15990900 -2.03230500 O -2.31266900 -3.76828800 -0.73333200 H -2.64208800 -4.41831800 -1.35980500 C -0.28093200 -0.62118500 -1.25032500 H 0.51302300 -1.07904300 -1.84186200 H -0.96629100 -0.08634800 -1.92132200 3C Ewater = -1391.088156 zero-point correction = 0.312258 C 1.35347100 0.40764900 1.33140900 C 1.07781800 -0.87248300 0.53560300 C -0.12735600 -0.65086300 -0.40977500 C 0.28946300 1.86201300 -0.44055100 C 1.51727700 1.65413200 0.45440700 H -0.24538200 -1.52910700 -1.05104400 H 0.80940500 -1.67346200 1.22846800 H 0.48904300 0.57631700 1.97949800 H -0.60082800 2.00161300 0.18104900 H 2.40691400 1.53060700 -0.18834900 O -1.25644200 -0.52314300 0.44236900 P -2.76309000 -0.20590900 -0.22390800 O -2.88704300 -1.03684300 -1.45718900 O -3.65667700 -0.83367300 0.98944100 C -3.69049300 -2.24711400 1.13698600 H -2.71796800 -2.62920900 1.46805400 H -4.44336000 -2.47464600 1.89735800 H -3.95665100 -2.73253800 0.19357200 O -2.97426400 1.26595400 -0.21736400 N 2.29224900 -1.27452400 -0.18343200 H 3.08951100 -0.66826900 -0.06451000 C 2.55922900 -2.56702800 -0.52212700 O 1.74863900 -3.47693300 -0.42840900 C 3.96274400 -2.81840100 -1.06340400 H 4.58699100 -1.92262400 -1.10216500 H 4.44885700 -3.56782300 -0.43472400 H 3.87736000 -3.23553500 -2.06921300 O 1.77992600 2.72816500 1.37185600 H 1.52168900 3.55266100 0.93545100 O 2.53430400 0.21971900 2.12712900 H 2.71607900 1.08103100 2.52371300 C 0.40919100 3.06660800 -1.36433600 H 1.24383400 2.93323300 -2.06828500 H -0.52115000 3.16545000 -1.93203300 O 0.63478700 4.26640000 -0.58473100

S8

H 0.57847500 5.03385400 -1.15973200 C 0.07871100 0.59293100 -1.28705600 H -0.79582400 0.70879300 -1.93017600 H 0.94743500 0.41812200 -1.93604600 3D Ewater = -1391.088252 zero-point correction = 0.312608 C -1.57872200 -0.05908400 1.33886500 C -0.75471900 1.05242300 0.67962600 C 0.33599400 0.41421700 -0.21486400 C -1.06555800 -1.68061800 -0.54149200 C -2.16149400 -1.05959300 0.33430300 H 0.87921000 1.20930500 -0.72986900 H -0.24498800 1.62938100 1.45603600 H -0.91107900 -0.60528000 2.00976500 H -0.37958100 -2.24031000 0.10244900 H -2.87540400 -0.53330600 -0.32137800 O 1.20067600 -0.26971600 0.68848200 P 2.73901300 -0.68781600 0.24874300 O 2.74421900 -1.15035500 -1.17465200 O 3.36574500 0.84073400 0.29247500 C 4.66040900 1.02333300 -0.25101300 H 4.88452000 2.09347400 -0.21103000 H 5.41628100 0.48020500 0.33098900 H 4.70322800 0.68088500 -1.29124200 O 3.28808800 -1.50396700 1.35905800 N -1.67128600 1.93624700 -0.05368500 H -2.64825100 1.77773000 0.14659300 C -1.34046500 3.18187000 -0.49636200 O -0.20126400 3.62233900 -0.51680700 C -2.51297000 4.01744600 -1.00329800 H -3.47103100 3.49298900 -0.98114900 H -2.58520700 4.92032000 -0.39224200 H -2.30011300 4.32866800 -2.02813300 O -2.89739000 -2.00736600 1.12627200 H -2.96739300 -2.82405700 0.61193300 O -2.64944300 0.53826100 2.09000200 H -3.19465100 -0.19828200 2.39352500 C -1.61548000 -2.63192400 -1.59624100 H -2.30406100 -2.09811600 -2.26638300 H -0.78575700 -3.02842100 -2.19045800 O -2.32156700 -3.72300700 -0.95645200 H -2.65455100 -4.32137300 -1.63083300 C -0.26954000 -0.55810800 -1.23422400 H 0.55800900 -0.97930000 -1.80787900 H -0.92262400 0.00383900 -1.91486800

3E Ewater = -1391.087419 zero-point correction = 0.312407 C 1.28814400 0.79058600 1.31993400 C 1.43338800 -0.57276300 0.63571700 C 0.18085500 -0.85416100 -0.22909900 C -0.27027000 1.64089300 -0.48834300 C 0.98345000 1.93319200 0.34495200 H 0.32677800 -1.78129600 -0.78624400 H 1.48698400 -1.35330200 1.39871800 H 0.45021500 0.71530300 2.01807700 H -1.13418700 1.55655800 0.17785600 H 1.83952600 2.05693400 -0.34067100 O -0.88257900 -1.01657200 0.70509800 P -2.36567000 -1.56678900 0.22460600 O -3.01574200 -2.21386900 1.39099700 O -3.05158600 -0.05966300 0.01131600 C -4.45638400 -0.03638300 -0.17272600 H -4.96979900 -0.50520100 0.67390700 H -4.76357700 1.01187900 -0.24693800 H -4.74698700 -0.55853300 -1.09390800 O -2.23204700 -2.20866500 -1.11515800 N 2.67868900 -0.58574700 -0.14252800 H 3.25611600 0.23481200 -0.03488600 C 3.32287900 -1.73279600 -0.50219600 O 2.84200100 -2.84933000 -0.38781300 C 4.71345900 -1.53308100 -1.09741300 H 5.02110500 -0.48649200 -1.15766400 H 5.43422500 -2.08485500 -0.48972200 H 4.72682000 -1.96598500 -2.10001800 O 0.89116400 3.11393100 1.15957100 H 0.36270700 3.76153500 0.67185200 O 2.49880400 1.08547900 2.03547000 H 2.39309300 1.98754100 2.36238700 C -0.56433600 2.72481200 -1.51712500 H 0.27498500 2.82020400 -2.22075200 H -1.46307400 2.45137000 -2.07986000 O -0.77619300 3.99429400 -0.85167200 H -0.94547500 4.67138200 -1.51246200 C -0.09158700 0.29228900 -1.21018100 H -0.98960400 0.04047700 -1.77683800 H 0.74622100 0.34936900 -1.91782000 3F Ewater = -1391.088413 zero-point correction = 0.313732 C -2.14284400 0.71216600 -0.01791200 C -0.68300800 0.82742100 0.47030900

S9

C 0.07925100 -0.50614400 0.34648100 C -2.11981800 -1.80526800 0.48377900 C -2.88591800 -0.47281700 0.59935000 H 0.20792200 -0.73325700 -0.71565700 H -0.71636300 1.11965800 1.52463800 H -2.66422700 1.63348000 0.25387600 H -2.66250900 -2.51666000 1.12398100 H -3.85286700 -0.56520500 0.09401100 O 1.36693500 -0.40011100 0.95608300 P 2.71339300 -0.26213300 -0.00191200 O 3.86809400 -0.10491600 0.91076500 O 2.74759300 -1.74209800 -0.71603100 C 3.26521200 -2.83505400 0.03212800 H 2.59807300 -3.10175900 0.86153900 H 3.34235100 -3.68574600 -0.65081900 H 4.24923700 -2.59487200 0.44293300 O 2.37914500 0.69158000 -1.11111800 N 0.02806900 1.85233700 -0.29893900 H 0.93114700 1.54145600 -0.70829900 C -0.13143500 3.17998900 -0.04539200 O -1.02161000 3.63878200 0.66695900 C 0.87005800 4.08550500 -0.74754700 H 1.67489300 3.52994500 -1.23069000 H 0.34187600 4.68885500 -1.49140600 H 1.29129100 4.76945200 -0.00783200 O -3.10620800 -0.12623500 1.97678900 H -3.54345400 -0.86994700 2.40250400 O -2.20597900 0.53279400 -1.44641700 H -1.50898000 1.08976200 -1.82066500 C -2.10653100 -2.40847000 -0.94659200 H -1.22999400 -2.05464000 -1.49492600 H -2.02233800 -3.49573300 -0.86547100 O -3.28212000 -2.15505300 -1.71236500 H -3.21225200 -1.23027800 -1.99022400 C -0.68724100 -1.64668500 1.02676500 H -0.12038800 -2.57275600 0.88648200 H -0.71396700 -1.44792400 2.10176100 3G Ewater = -1391.086792 zero-point correction = 0.312355 C 1.80897800 1.25229400 0.25900300 C 0.47240900 0.96149400 -0.45646000 C 0.15480800 -0.54026200 -0.46479000 C 2.63869900 -1.10715200 -0.42243500 C 2.96941400 0.39145400 -0.26189400 H 0.02998000 -0.89696500 0.56189500 H 0.56580100 1.31344400 -1.48864900 H 2.06924500 2.29959400 0.08104700 H 3.43038500 -1.54118900 -1.05122000 H 3.79859000 0.49809400 0.44578900

O -1.06536900 -0.75043500 -1.17525900 P -2.28003400 -1.58202000 -0.44140100 O -1.71151000 -2.67621200 0.39735800 O -2.71014100 -0.33469000 0.61223300 C -3.66502100 -0.66086000 1.61192100 H -3.31971500 -1.50500100 2.21812300 H -3.79514500 0.21768700 2.25147400 H -4.62934700 -0.91784000 1.15867200 O -3.36541500 -1.77207100 -1.42988500 N -0.63581700 1.67583500 0.19142100 H -1.44474500 1.09442900 0.42140600 C -0.86569300 3.00253300 -0.01953700 O -0.05580400 3.75856200 -0.54496100 C -2.21553400 3.51007400 0.46828100 H -2.76158200 3.90620800 -0.39119600 H -2.82033200 2.73718000 0.94449000 H -2.05289800 4.33510000 1.16569300 O 3.33935900 0.97317300 -1.52545300 H 4.02823700 0.42284900 -1.91011100 O 1.70111700 1.01750800 1.67143400 H 0.84163100 1.37212100 1.93394300 C 2.72251300 -1.86717200 0.90480100 H 2.11275200 -1.38194100 1.66835200 H 2.35535600 -2.88953800 0.75865000 O 4.10275200 -1.90435600 1.32343100 H 4.12380900 -1.95304700 2.28228900 C 1.28902500 -1.31598900 -1.13278300 H 1.01847900 -2.37481500 -1.14352100 H 1.36322400 -0.98723000 -2.17386700 3H Ewater = -1391.086352 zero-point correction = 0.312379 C -1.88640500 1.06381500 -0.09813100 C -0.46077300 0.92120500 0.49111800 C 0.05257000 -0.52817000 0.39963500 C -2.36866500 -1.40117300 0.52440100 C -2.88674300 0.05460500 0.49586900 H 0.15839500 -0.78140600 -0.66435200 H -0.52951900 1.18234300 1.55641000 H -2.22864100 2.07077900 0.14880100 H -3.02471900 -1.96568000 1.20693900 H -3.79925500 0.09628200 -0.11147000 O 1.30193600 -0.65998100 1.05098300 P 2.76352900 -0.67097200 0.27246300 O 3.78863500 -0.28056700 1.27827300 O 2.99644600 -2.26612400 -0.03901700 C 2.31393200 -2.90839000 -1.09717000 H 2.39959900 -2.33320900 -2.02664200 H 2.76825100 -3.89753100 -1.22409100 H 1.24554700 -3.04717000 -0.86757500

S10

O 2.55050900 0.02723000 -1.06262100 N 0.48385700 1.80994200 -0.16553100 H 1.31146300 1.36388700 -0.57547100 C 0.32953900 3.13988400 -0.22658800 O -0.67887100 3.74164000 0.17122300 C 1.47530100 3.88783700 -0.91183700 H 2.19140600 4.21940800 -0.15214300 H 2.02851400 3.26447900 -1.62085100 H 1.07742500 4.77559200 -1.41217100 O -3.16173300 0.51617000 1.83138200 H -3.85182400 -0.06525000 2.18917200 O -1.87049600 0.89097700 -1.53373700 H -1.73175900 1.75704100 -1.93577300 C -2.51276400 -2.09948300 -0.83287300 H -2.05806900 -1.49622800 -1.62229100 H -2.01600300 -3.08162500 -0.79690900 O -3.92276500 -2.28198100 -1.09022100 H -4.02057200 -2.40566600 -2.04666700 C -0.93655000 -1.47242300 1.08888600 H -0.55331300 -2.49876100 1.02445000 H -0.95280500 -1.20745700 2.15242100

S11

1H NMR Spectrum of compound 2

1.01.52.02.53.03.54.04.55.0 ppm

S12

13C NMR Spectrum of compound 2

2030405060708090100110120130140150160170180 ppm

S13

31P NMR Spectrum of compound 2

-1090 80 70 60 50 40 30 20 10 0 ppm

S14

1H NMR Spectrum of compound 3

1.01.52.02.53.03.54.04.5 ppm

S15

13C NMR Spectrum of compound 3

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

S16

31P NMR Spectrum of compound 3

-30-25-20-15-10-535 30 25 20 15 10 5 0 ppm

S17

1H NMR spectrum of compound 6

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5 ppm

S18

13C NMR spectrum of compound 6

200 180 160 140 120 100 80 60 40 20 0 ppm1

S19

1H NMR spectrum of compound 7

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

S20

HSQC NMR spectrum of compound 7

ppm

8 7 6 5 4 3 2 1 ppm

160

140

120

100

80

60

40

20

S21

1H NMR spectrum of compound 8

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 ppm

S22

13C NMR spectrum of compound 8

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

S23

1H NMR spectrum of compound 9

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

S24

13C NMR spectrum of compound 9

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

S25

1H NMR spectrum of compound 10

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 ppm

S26

13C NMR spectrum of compound 10

170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm

S27

HSQC NMR spectrum of compound 10

ppm

8 7 6 5 4 3 2 1 ppm

120

100

80

60

40

20

S28

31P NMR Spectrum of compound 10

-1090 80 70 60 50 40 30 20 10 0 ppm