A general strategy for synthesis of both (6Z)- and (6E)-cladiellin diterpenes: total syntheses of (-)-cladiella-6,11-dien-3-ol, (+)-polyanthellin A, (-)-cladiell-11-ene-3,6,7-triol, and (-)-deacetoxyalcyonin acetate

The first total synthesis of an (E)-cladiellin diterpene, (-)-cladiella-6,11-diene-3-ol (1), was accomplished featuring an intramolecular amide enolate alkylation-intramolecular Diels-Alder strategy. In addition, a highly stereo-, regio-, and chemoselective synthetic strategy for other members of the cladiellin diterpenes such as (+)-polyanthellin A (2), (-)-cladiell-11-ene-3,6,7-triol (3), and (-)-deacetoxyalcyonin acetate (4) was developed utilizing the synthetic (E)-cladiellin 1 as a common intermediate by taking advantage of the unique chemical properties of its C(6)-(E)-oxatricyclic skeleton.     

Stereochemical and mechanistic aspects of the nickel complex catalysed formation of olefins from allylic alcohols and Grignard reagents

The reaction of (+)-S-but-1-en-3-ol with phenylmagnesium bromide in the presence of bis(triphenylphosphine)nickel dichloride has been shown to proceed with inversion of configuration to yield (?)-R-3-phenylbut-1-ene.     

Carbonylation of (+)-2-carene induced by iron-pentacarbonyl.

(+)-2-carene heated neat with iron pentacarbonyl leads to α-phellandrene-Fe(CO)₃ complex ( ～15 % ), p. cymene ( ～15 % ), (-)-(1S)-3,8,8-trimethylbicyclo (4.1.1) oct-3-ene-7-one ( ～50 % ) and (+)-(1S,7S)-3,8,8-trimethylbicyclo (4.1.1.) oct-3-ene-7-ol ( ～20 % ).     

Enantioselective synthesis of the bisabolane sesquiterpene (+)-1-hydroxy-1,3,5-bisabolatrien-10-one and revision of its absolute configuration

The enantioselective synthesis of (S)-1-hydroxy-1,3,5-bisabolatrien-10-one 1 is here described. This sesquiterpene was prepared using (S)-3-(2-methoxy-4-methyl-phenyl)butan-1-ol as a chiral building block. Two different pathways were employed and both turned out to be high yielding, affording 1 in good chemical purity and without any racemization of the existing stereocenter. The spectroscopic data of the synthetic (S)-1 were in very good agreement with those reported for the natural compound, which was extracted from Juniperus formosana heartwood and from the leaves of J. chinensis. The positive sign of the measured optical rotation value of synthetic (S)-1 allows the unambiguous assignment of the absolute configuration of (+)-1 as the (S)-enantiomer. This finding corrects the previous configuration determination which indicated the opposite result. At last, since even (R)-3-(2-methoxy-4-methyl-phenyl)butan-1-ol is preparable in high enantiomer purity by mean of a different biocatalytic process, the formal synthesis of natural (R)-1 was also accomplished.     

Solution Structure of One-Electron Reduced and Oxidized Molecules with Twisted Donor and Acceptor Moieties

The solution structures of the radical anion and the radical cation of the donor-acceptor molecules 3,4-di(1,3-dithiol-2-ylidene)-4-phenylbut-1-ene-1,1-dicarbonitrile ( 1 ) and 3,4-di(1,3-dithiol-2-ylidene)-4-phenylbut-1-ene-1,1,2-tricarbonitrile ( 2 ) are discussed based on cyclovoltammetric and ESR/ENDOR measurements. It is shown that the spin population of the radical anions is limited to the di- and tricyanoethene moiety and the coplanar 1,3-dithiole at C(3), whereas that of the radical cations resides mainly inside the two 1,3-dithiole rings. The energies of the long-wave bands in the electronic-absorption spectra of 1 and 2 correspond to the differences between the oxidation and reduction potentials and thus point to a charge-transfer character of these transitions.     

Synthesis of a C(29)-C(51) subunit of spongistatin 1 (Altohyrtin A) starting from (R)-3-benzyloxy-2-methylpropan-1-ol

A protected C(29)-C(51) subunit ((+)-38) of spongistatin 1 has been obtained. Key steps involve the aldol condensation of (3S, 4R)-3-methyl-7-[(p-methoxybenzyl)oxy]-4-[(triethylsilyl)oxy]octan- 2-o ne ((-)-6) with (tert-butyl)dimethylsilyl 4-deoxy-2, 3-di-O-(methoxymethyl)-4-methyl-6-O-(tert-butyl)dimethylsilyl)-bet a-D -glycero-L-gluco-heptodialdo-1,5-pyranoside ((+)-7) and a C-glycosidation of (4R,7R&S,E)-7, 8-dichloro-2-methylidene-1-(trimethylsilyl)oct-5-en-4-yl p-methoxybenzoate (16). Aldehyde (+)-7 was derived from (R)-3-benzyloxy-2-methylpropan-1-ol ((+)-10) in 13 formal steps but requiring the isolation of five intermediate products only. The longest linear synthetic scheme converts (+)-10 into (+)-38 in 2% overall yield (isolation of 11 intermediate products).     

Synthesis of (-)-fortamine and (+)-2-deoxyfortamine from resolved 3S,4S-N-carbomethoxy-3-aminocyclohexen-4-ol

A three step sequence (Scheme I) starting with racemic 3,4-epoxycyclohexene (5) and (S)-α-methylbenzylamine gave 3S,4S-N-carbomethoxy-3-aminocydohexen-4-ol (10) with chromatographic removal of the undesired 3R,4R byproduct. The absolute configuration of 10 was established by x-ray crystallographic analysis of its precursor, 6 (as the HCl salt). Resolved 10 was converted to the aminocyditols (-)-fortamine (1) and (+)-2-deoxyfortamine (2) by efficient routes which parallel those previously developed in the racemic series.     

昆虫性信息的结构鉴定与合成 XXVII: (5R, 6S)-(-)-及(5S, 6R)-(+)-淡色库蚊产卵引诱性信息素的立体选择性合成与手性亚砜不对称加成的立体化学

从R-(-)-正十三烯-3-醇2所得的R-(+)-醛5, 与R-(+)亚砜化合物6的不对称醇醛缩合得7a和7b(30:1). 7a经一系列转化得1a, 从(5S, 6R)-14出发, 经两次构型翻转[5S,6R)-15→(5S, 6S)-16和(5S, 6S)-17→(5R, 6S)-14], 得1a的对映体1b. 光学活性α-苄氧基醛5与手性亚砜的不对称醇醛缩合, 受手性亚砜的1,3-不对称诱导控制, 而不是受醛5的1,2-不对称诱导控制.     

New steroidal sapogenins from the acid hydrolysis product of the whole glycoside mixture of Welsh onion seeds

Two new steroidal sapogenins(1,2) along with five known steroidal sapogenins were isolated from the acid hydrolysis product of the whole glycoside mixture of Welsh onion(Allium fistulosum L.) seeds.Based on comprehensive spectroscopic analyses, including 2D NMR spectroscopy and mass spectrometry,their structures were elucidated as(25R)-19-norspirosta-l,3,5(10)-triene-4 -methyl-2-ol(1),(25R)-spirost-l,4-diene-3-one-2,6-diol(2),(25R)-spirost-l,4-diene-3-one-2-ol(3),(25R)-spirost-4-ene-3-one-2-ol (4),yuccagenin(5),gitogenin(6) and tigogenin(7).     

Stereochemistry of amino-carbonyl compounds—VII: Absolute and ralative configuration of some diastereomeric 1,3-amino-alcohols.

The absolute configuration of (+)-4-dimethylamino-2,4-diphenyl-butan-2-ol and (+)-4-piperidino-2-phenyl-pentan-2-ol, the predominant diastereomers obtained by reaction of (+)-3-dimethylamino-1,3-diphenyl-propan-1-one with MeLi and (+)-3-piperidino-1-phenyl-butan-1-one with MeMgI, respectively, was determined by chemical correlation. The relative configurations of the diastereomers afforded by such reactions were thus assigned.     

Absolute configuration of (−)-4-methylheptan-3-ol,a pheromone of the smaller european elm bark beetle,as determined by the synthesis of its (3R,4R)-(+)- and (3S,4R)-(+)-isomers

Nerol and geraniol were stereoselectively converted to (±)-threo- and (±)-erythro-4-methylheptan-3-ol respectively. (R)-(+)-Citronellic acid was converted to a mixture of (3R,4R)-(+)-threo- and (3S,4R)-(+)-erythro-isomers which was separable by GLC. These syntheses established the absolute configuration of the naturally occurring (?)-4-methylheptan-3-ol to be 3S,4S.     

Synthesis and biological activities of optical isomers of 2-(4-diphenylmethyl-1-piperazinyl)ethyl 5-(4,6-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dim ethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate dihydrochloride (NIP-101).

Six optical isomers of 2-(4-diphenylmethyl-1-piperazinyl)ethyl 5-(4,6-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate dihydrochloride (NIP-101, 1.2HCl.2H2O), a potent calcium antagonist, were successfully prepared by using optically active (2R,4R)-(-)- and (2S,4S)-(+)-2,4-pentanediols, and cis-2,4-pentanediol and optically active (S)-(+)-2-methoxy-2-phenylethanol. Their proton nuclear magnetic resonance investigations demonstrate that the 1,3,2-dioxaphosphorinane group is conformationally constrained around the C-P bond. Calcium-antagonistic and hypotensive activities of the optical isomers were examined and found to depend mainly on the absolute configuration at a stereogenic center in the 1,4-dihydropyridine ring rather than the configuration of the 1,3,2-dioxaphosphorinane moiety.     

Bretonin A and Isobretonin A,Unique Glycerol Derivatives Isolated from a Demosponge of Brittany Waters

It is shown that an unidentified marine demosponge of Brittany contains two unique lipids consisting of glycerol etherified by a C₁₂ trienic linear alcohol and esterified by 4-hydroxybenzoic acid. The latter is attached to the secondary position of glycerol in bretonin A (= 3-[((4E, 6E, 8E)-dodeca-4,6,8-trienyl)oxy]-2-(4-hydroxy-benzoyl)propan-1-ol; 1a ), and to the other primary position of glycerol in isobretonin A ( = (+)-3-[((4E, 6E, 8E)-dodeca-4,6,8-trienyl)oxy]-1-(4-hydroxybenzoyl)propan-2-ol; (+) -2 ). The structures are based on NMR and MS data, including the ones of the acetylation product (?)- 1b of 1a .     

Palladium(0)-catalyzed enantioselective O,S-rearrangement of racemic O-allylic thiocarbamates: a new entry to enantioenriched allylic sulfur compounds

Reaction of (+/-)-(E)-pent-3-en-2-ol, (+/-)-(E)-hept-4-en-3-ol, (+/-)-(E)-2,6-dimethylhept-4-en-3-ol, (+/-)-cyclohex-2-en-1-ol, and (+/-)-cyclohept-2-en-1-ol with methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, and benzyl isothiocyanate gave the corresponding racemic O-allylic thiocarbamates of medium to good thermal stability in good yields. The palladium(0)-catalyzed rearrangement of the (+/-)-(E)-pent-3-en-2-ol-, (+/-)-(E)-hept-4-en-3-ol-, (+/-)-cyclohex-2-en-1-ol-, and (+/-)-cyclohept-2-en-1-ol-derived O-allylic thiocarbamates at room temperature in methylene chloride by using Pd2(dba)3*CHCl3 (dba = dibenzylideneacetone) as precatalyst and (+)-(1R,2R)-1,2-bis-N-((2-(diphenylphosphino)benzoyl)-1,2-diaminocyclohexane as ligand for the palladium atom proceeded quantitatively and gave the corresponding acyclic (R)-configured S-allylic thiocarbamates and the cyclic (S)-configured S-allylic thiocarbamates with ee values ranging from 85% to > or = 99% in yields of 76-94%. Rearrangement of the O-allylic thiocarbamates carrying a methyl group at the N atom not only was the fastest but also proceeded with the highest enantioselectivity. No rearrangement was observed under these conditions in the case of the racemic N-methyl O-allylic thiocarbamate derived from (+/-)-2,6-dimethylhept-4-en-3-ol, which has a branched carbon skeleton. (S)-cyclohex-2-enethiol of 97% ee was obtained through hydrolysis of the corresponding N-methyl S-allylic thiocarbamate. 2-((R)-(E)-1-methylbut-2-enylsulfanyl)pyrimidine of 91% ee and 2-((S)-cyclohex-2-enylsulfanyl)pyrimidine of 97% ee were synthesized in one synthetic operation from the corresponding N-methyl S-allylic thiocarbamates and 2-chloropyrimidine. Similarly, (S)-cyclohex-2-enylsulfanyl)benzene of 97% ee was obtained in one synthetic operation from the corresponding N-methyl S-allylic thiocarbamate through a palladium(0)-catalyzed substitution of iodobenzene in the presence of a base. The palladium(0)-catalyzed enantioselective rearrangement of O-allylic carbamates to S-allylic carbamates has been extended from the solution phase to the solid phase by using a methyl thioisocyanate polystyrene resin. In the case investigated the enantioselectivity of the rearrangement on the solid phase was considerably lower than that in solution.     

A Chemical Study of Burley Tobacco Flavour (Nicotiana tabacum L.) VII. Identification and synthesis of twelve irregular terpenoids,related to solanone,including 7,8-dioxabicyclo[3.2.1]octane and 4,9-dioxabicyclo[3.3.1]nonane derivatives

Twelve novel constituents isolated from Burley tobacco condensate by semi-preparative GLC. have been identified as (E)-3,4-epoxy-5-isopropyl-nonane-2,8-dione ( A ), exo-(1-methyl-4-isopropyl-7,8-dioxabicyclo[3.2.1]oct-6-yl)methyl ketone ( B ), exo-1-(1-methyl-4-isopropyl-7,8-dioxabicyclo[3.2.1]oct-6-yl)-ethanol ( C ), (E)-5-isopropyl-8-hydroxy-8-methyl-non-6-en-2-one ( D ), (E)-5-isopropyl-6,7-epoxy-8-hydroxy-8-methyl-nonan-2-one ( E ), endo-2-(1-methyl-4-isopropyl-7,8-dioxabicyclo[3.2.1]oct-6-yl)-propan-2-ol ( F ), 3,3,5-trimethyl-8-isopropyl-4,9-dioxabicyclo[3.3.1]nonan-2-ol ( G ), (E)-5-isopropyl-non-3-ene-2,8-diol ( H ), 5-isopropyl-nonane-2,8-diol ( I ), (E)-5-isopropyl-8-hydroxy-non-6-en-2-one ( J ), 5-isopropyl-8-hydroxy-nonan-2-one ( K ), and (E)-3-isopropyl-6-methyl-hepta-4,6-dien-1-ol ( L ). Compounds A–K were synthesized from norsolanadione ( 2 ), and compound L from 2-isopropyl-5-oxo-hexanal ( 15 ). The relative configuration of the bicyclic internal acetals B, C, F, G and their δ-keto-epoxide precursors A and E is discussed. All these Burley tobacco flavour components belong to a growing family of metabolites structurally related to solanone ( 1 ). They are believed to arise from the breakdown of cembrene-type precursors.     

Gold versus silver-catalyzed amination of allylic alcohols

Direct substitution of the hydroxy group in allylic alcohols by different nitrogenated nucleophiles is performed using low loadings of cationic gold(I) or silver salts as catalysts. Sulfonamides, carbamates and aromatic amines can be used as nucleophiles. Comparative studies between the best catalysts, cationic (triphenylphosphite)gold(I) complex and silver triflate, demonstrate that the former catalyst shows, in general, better performance than silver, working at lower loadings, in shorter reaction times and at lower temperatures. Representative allylic alcohols are used giving good γ-regioselectivity, specially in the case of penta-1,4-dien-3-ol and (E)-1-phenylbut-2-en-1-ol affording the corresponding allylic sulfonamides with total regio and stereoselectivity by a hydroamination mechanism. In the case of crotyl alcohol and (E)-4-phenylbut-3-en-2-ol mainly and exclusively α-substituted sulfonamides were obtained, respectively, by a cationic mechanism.     

1,5-Benzoxathiepin derivatives. III. Optical resolution of methyl (+/-)-cis-3-hydroxy-4-[3-(4-phenyl-1-piperazinyl)propyl]-3,4-dihydro- 2H-1,5-benzoxathiepin-4-carboxylate hydrochloride ((+/-)-CV-5197) with selective 5-hydroxytryptamine2(5-HT2)-antagonistic activity

The selective 5-HT2-receptor antagonist, methyl (+/-)-cis-3-hydroxy-4-[3-(4-phenyl-1-piperazinyl)propyl]-3,4-dihydro-2H- 1,5-benzoxathiepin-4-carboxylate hydrochloride ((+/-)-CV-5197) was resolved in high optical purity using (R)-(-)- and (S)-(+)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphates ((R)-(-)- and (S)-(+)-BNP). The absolute configuration of (+)-CV-5197 was determined to be 3S,4R by X-ray crystallographic analysis. In the binding assay, it was demonstrated that (+)-CV-5197 was a more active isomer (IC50 = 23 nM +/- 6.3) for 5-HT2 receptor binding than the (-)-enantiomer (IC50 = 1600 nM +/- 82). (+)-CV-5197 completely inhibited the 5-HT-induced contraction of the isolated pig coronary artery at a concentration of 3 x 10(-7) M, whereas (-)-CV-5197 showed little antagonistic activity, even at 3 x 10(-4) M. Thus, the agreement between the results of the binding assays and the biological activities for the 3S,4R enantiomer of CV-5197 suggests that its physiological activity is probably exerted through 5-HT2-receptor antagonism.     

The heterocyclic ring fission and dehydroxylation of catechins and related compounds by Eubacterium sp. strain SDG-2, a human intestinal bacterium.

A human intestinal bacterium, Eubacterium (E.) sp. strain SDG-2, was tested for its ability to metabolize various (3R)- and (3S)-flavan-3-ols and their 3-O-gallates. This bacterium cleaved the C-ring of (3R)- and (3S)-flavan-3-ols to give 1,3-diphenylpropan-2-ol derivatives, but not their 3-O-gallates. Furthermore, E. sp. strain SDG-2 had the ability of p-dehydroxylation in the B-ring of (3R)-flavan-3-ols, such as (-)-catechin, (-)-epicatechin, (-)-gallocatechin and (-)-epigallocatechin, but not of (3S)-flavan-3-ols, such as (+)-catechin and (+)-epicatechin.     

Beyerane derivatives and a sesquiterpene dimer from Japanese Cypress (Chamaecyparis obtusa)

In the course of studies on biological active constituents from woody plants, we previously reported the isolation of many lignan derivatives as neurite outgrowth-promoting compounds from an ethyl acetate soluble fraction of Japanese Cypress (Chamaecyparis obtusa). Further chemical investigation on the residual parts of the ethyl acetate soluble fraction of a methanol extract of Japanese Cypress resulted in the isolation of four new beyerene type derivatives and a novel sesquiterpene dimer formed between cryptomeridiol and hinokiic acid. Their structures were elucidated as 18-O-(Z)-p-coumaroylbeyer-15-ene-18-ol (1), 18-O-(E)-p-coumaroylbeyer-15-ene-18-ol (2), 18-O-(E)-p-coumaroylbeyer-15-ene-11beta,18-diol (3), 18-O-(Z)-p-coumaroylbeyer-15-ene-11beta,18-diol (4) and ent-cryptomeridiol-4-yl-hinokiiate (5) by (1)H-NMR, (13)C-NMR, 2D-NMR, and HR-MS spectral analysis.     

Megastigmane glucosides from Equisetum debile and E. diffusum

A new megastigmane diglucoside, (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3,9-O-beta-D-diglucopyranoside (3), was isolated from the aerial portion of Equisetum debile along with macarangioside D (debiloside A), sammangaoside A, (6R,9S)-3-oxo-alpha-ionol 9-O-beta-D-glucopyranoside, debiloside B, kaempferol 3-O-sophoroside, kaempferol 3,7-O-beta-D-diglucopyranoside, kaempferol 3-O-sophoroside-7-O-beta-D-glucopyranoside, phenylethyl O-beta-D-glucopyranoside, (Z)-3-hexenyl O-beta-D-glucopyranoside, (7S,8R)-dehydrodiconiferyl 4-O-beta-D-glucopyranoside, and L-tryptophan. The absolute configuration at C-6 of the original structure of debilo-side A was revised to 6R-configuration, and was identical with macarangioside D (1). From the aerial portion of E. diffusum, four compounds, sammangaoside A, kaempferol 3-O-sophoroside and L-tryptophan and (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3-O-beta-D-glucopyranoside were identified. The spectroscopic data of (3S,5R,6S,7E,9S)-megastigman-7-ene-5,6-epoxy-3,9-diol 3-O-beta-D-glucopyranoside (13) were found to be identical with corchoionoside A (9R-isomeric compound). The structure of corchoionoside A was also discussed. Structure determinations were based on physical data and spectroscopic evidence.