From oxides of internal perfluoroolefins to fluorocontaining camphor thiazolinylhydrazones

The reaction of oxides of internal trans- and cis-perfluoroolefins with (1S, 4S)- or racemic camphor thiosemicarbazone leads to the formation of trans- and cis-isomers of (1S, 4S)- or racemic camphor 5′-fluoro-4′-hydroxy-4′,5′-di(perfluoroalkyl)-1′,3′-thiazolinyl-2′-hydrazones, respectively. Unsymmetrical dodecafluoro-2,3-epoxyhexane yields a mixture of regioisomeric hydrazones. The molecular structure of the trans-isomer of (1S, 4S)-camphor 5′-fluoro-4′-hydroxy-4′,5′-bis(trifluoromethyl)-1′,3′-thiazolinyl-2′-hydrazone has been established by X-ray crystallography. The quite rare example of cocrystallization of two diastereomers of the latter in homochiral crystal (sp. group P2₁) has been revealed.     

Synthesis,NMR spectra and chromatographic properties of five trimethylarsonioribosides

Five trimethylarsonioribosides were prepared from naturally occurring and synthetic dimethylarsinylribosides (arsenosugars) by reducing them with 2,3-dimercaptopropanol and quaternizing the resultant arsine with methyl iodide. The trimethylarsonioribosides prepared in this manner were the four novel compounds methyl 5-deoxy-5-trimethylarsonio-β-D -riboside (as the iodide), (2′R)-2′, 3′-dihydroxypropyl 5-deoxy-5-trimethylarsonio-β-D -riboside (as the formate), 3′-[(2″, 3″ -dihydroxypropyl)hydroxyphosphinyloxy] - 2′ -hydroxypropyl 5-deoxy-5-trimethylarsonio-β-D -riboside and 3-(5′-deoxy-5′-trimethylarsonio-β-D -ribosyloxy)-(2S)-2-hydro xypropanesulfonate, and the known (2′S)-2′-hydroxy-3′-(sulfooxy)propyl 5-deoxy-5-trimethylarsonio-β-D -riboside. They were synthesized to serve as standards for chromatographic analyses of arsenic compounds in marine samples and for investigations into the biotransformation of arsenic in marine organisms. NMR spectral and chromatographic data for the five trimethylarsonioribosides are presented and compared with those of their dimethylarsinyl analogues.     

Abnormal Beckmann rearrangement in 23-hydroxyiminodiosgenin acetate

A new transformation of the spiroketal side chain of diosgenin is reported: treatment of 23-hydroxyiminodiosgenin acetate with phosphorous oxychloride in pyridine produced an abnormal Beckmann rearrangement directing to the cleavage of the spiroketal side chain and generating 23,24-bisnorchol-5-enic skeletons: (2′R)-3′-cyano-2′-methylpropyl 3β-acetoxy-16α-chloro-23,24-bisnorchol-5-en-22-oate as the main product, and small amounts of (2′R)-3′-cyano-2′-methylpropyl 3β-acetoxy-16β-hydroxy-23,24-bisnorchol-5-en-22-oate and vespertilin acetate.     

Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. Part 6: synthesis and incorporation into peptides of the first reported 2,3-dihydroxycyclopentanecarboxylic acid

Herein we report the intramolecular alkylation of nitronates of methyl-5-O-benzyl-3,6-deoxy-6-nitro-β-d-glucofuranoside and methyl-5-O-benzyl-3,6-deoxy-6-nitro-α-d-glucofuranoside into the corresponding 2-oxabicyclo[2.2.1]heptane derivatives. Similarly, methyl-3-O-benzyl-5-deoxy-5-nitromethyl-β-d-xylofuranoside and methyl-3-O-benzyl-5-deoxy-5-nitromethyl-α-d-xylofuranoside were cyclized to (1R,3R,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane and (1R,3S,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane, respectively. These 2-oxabicyclo[2.2.1]heptane derivatives were eventually transformed into enantiopure methyl (1S,2S,3R,4S,5R)-2-amino-2,3-dihydroxycyclopentanecarboxylate and this novel β-amino acid was incorporated into peptides.     

Latoxanthin, a minor carotenoid isolated from the fruits of yellow paprika (Capsicum annuum var. lycopersiciforme flavum)

Latoxanthin was isolated as a minor carotenoid from the ripe fruits of yellow tomato shaped paprika (Capsicum annuum var. lycopersiciforme flavum) and identified as (all-E,3S,5R,6R,3′S,5′R,6′S)-5′,6′-epoxy-5,6,5′,6′-tetrahydro-β,β-carotene-3,5,6,3′-tetrol based on spectral data.     

Formal synthesis of (−)-anisomycin based on stereoselective nucleophilic substitution along with 1,2-aryl migration

The stereoselective conversion of (4R)-5-hydroxy-4-(4′-methoxyphenyl)-2(E)-pentenoate 4 into the (4S)-4-hydroxy-5-(4′-methoxyphenyl)-2(E)-pentenoate 5 using the AgNO₃/MS 4 Å/MeNO₂ system was accomplished along with complete inversion at the C₄-position, and the synthesis of the intermediate (4S)-7 for the chiral synthesis of (−)-anisomycin 6 from (4S)-7 based on osmium tetroxide-catalyzed stereoselective hydroxylation was achieved.     

Trading N and O. Part 2: Exploiting aziridinium intermediates for the synthesis of β-hydroxy-α-amino acids

The β-hydroxy-α-amino acids (S,S)-allo-threonine, (S,S)-β-hydroxyleucine and a range of aryl substituted (S,S)-β-hydroxyphenylalanines were prepared from the corresponding enantiopure anti-α-hydroxy-β-amino esters via a rearrangement protocol, which proceeds via the intermediacy of the corresponding aziridinium ions. The starting anti-α-hydroxy-β-amino esters were prepared in >99:1 dr using our diastereoselective aminohydroxylation procedure, whereby conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to an α,β-unsaturated ester is followed by oxidation of the resultant enolate with (−)-camphorsulfonyloxaziridine. Subsequent activation of the hydroxyl group within the anti-α-hydroxy-β-amino esters promoted aziridinium ion formation [which proceeds with inversion of configuration at C(2)], and regioselective ring-opening of the intermediate aziridinium ions with H₂O [which proceeds with inversion of configuration at C(3)] gave the corresponding anti-β-hydroxy-α-amino esters as single diastereoisomers (>99:1 dr). Deprotection of these substrates via sequential hydrogenolysis and ester hydrolysis gave the corresponding β-hydroxy-α-amino acids in good yield and high diastereoisomeric and enantiomeric purity.     

Structures of bulgecins,bacterial metabolites with bulge-inducing activity

The structure of bulgecin A, a bacterial metabolite with bulge-inducing activity, was determined chemically and spectrometrically to be 4-o-(2'-acetylamino-2'-deoxy-4'-o-hydroxysulfonyl-β-D-glucopyranosyl)-(2S, 4S, 5R -4-hydroxy-5-hydroxymethylprolyltaurine monosodium salt. Bulgecns B and C, the minor components, were found to be analogs of bulgecin A in which the taurine moiety was replaced as shown in Fig, 1.     

The first synthesis of N,O-protected β-isoserines bearing two adjacent quaternary stereogenic centers and their corresponding β-lactams

The reaction of chiral (2S)-enolates of dioxolan-4-ones, derived from lactic and mandelic acids, with (S_R)-tert-butyl sulfinyl ketimines, derived from butan-2-one, pentan-2-one, and decan-2-one, afforded conformationally restrained β^2,2,3,3-isoserines bearing two adjacent quaternary stereogenic centers in the form of N-sulfinyl protected 1′-amino-dioxolan-4-ones. The selective acid-induced removal of the sulfinyl protecting group provided the corresponding 1′-aminodioxolanones, whose base-induced cyclization afforded the corresponding chiral tetra-substituted 3-hydroxy-β-lactams. The synthesis of a dipeptide by reaction coupling between the 1′-aminodioxolanone (2S,5R,1′R)-19 and N,N-dimethylglycine was successfully achieved.     

Synthesis and reactivity of 4″-phenylsulfinimine-avermectin B1 and 4′-phenylsulfinimine-avermectin B1 monosaccharide derivative

A short, efficient synthesis of 4″-(R or S)-4″-deoxy-4″-amino-4″-C substituted avermectin B₁ and 4′-(R or S)-4′-deoxy-4′-amino-4′-C substituted avermectin B₁ monosaccharide 3 and 4 has been developed through the nucleophilic addition of an organometallic reagent to an intermediate phenylsulfinimide 7. These new derivatives of avermectin B₁ exhibited potent, broad spectrum insecticidal activity.     

A general and efficient route to 3′-deoxy-3′-N-, S-, and C-substituted altropyranosyl thymines from 2′,3′-O-anhydro-mannopyranosylthymine

An efficient route to 1-(2,3-O-anhydro-4,6-O-phenylmethylene-β-d-mannopyranosyl) thymine from 1,2,4,6-tetra-O-acetyl-3-O-tosyl-β-d-glucopyranose has been devised. This newly synthesized epoxide is opened up regioselectively at the C-3′-position by N-, S-, and C-nucleophiles to afford a wide range of new 3′-deoxy-3′-substituted altropyranosyl thymines.     

Clerodane diterpenoids from Microglossa angolensis

Two new diterpenoids, 6β-(2-methylbut-2(Z)-enoyl)-3α,4α,15,16-bis-epoxy-8β,10βH-ent-cleroda-13(16),14-dien-20,12-olide and 10β-hydroxy-6-oxo-3α,4α,15,16-bis-epoxy-8βH-cleroda-13(16),14-dien-20,12-olide, together with the known β-amyrin, spinasterol, 5,7-dihydroxy-3,8,3′,4′-tetramethoxyflavone and 5,7-dihydroxy-3,8,3′,4′,5′-pentamethoxyflavone have been isolated from the aerial parts of Microglossa angolensis Oliv. et Hiern (Compositae). The structures were elucidated on the basis of spectral studies and comparison with published data.     

4-Ketoantheraxanthin, a novel carotenoid produced by the combination of the bacterial enzyme β-carotene ketolase CrtW and endogenous carotenoid biosynthetic enzymes in higher plants

Higher plants do not ordinarily possess ketocarotenoids due to the absence of a carotenoid ketolase enzyme. We expressed genes coding for marine-bacterial enzymes β-carotene ketolase (CrtW) and β-carotene hydroxylase (CrtZ) in tobacco plants (Nicotiana tabacum) by transplastomic engineering. A novel carotenoid, 4-ketoantheraxanthin, was isolated from the leaves of the tobacco transformants. The structure of 4-ketoantheraxanthin was determined to be (3S,3′S,5′R,6′S)-5′,6′-epoxy-3,3′-dihydroxy-β,β-caroten-4-one by analysis of the MS, NMR, and CD data. This carotenoid was considered to be synthesized by a 4-ketolation reaction by CrtW of antheraxanthin that had been synthesized by the endogenous carotenoid biosynthetic enzymes present in higher plants and CrtZ. 4-Ketoantheraxanthin was also shown to have potent antioxidative activity against a ¹O₂ suppression model.     

Polyhydroxylated pyrrolidines, III. Synthesis of new protected 2,5-dideoxy-2,5-iminohexitols from d-fructose

The readily available 3-O-benzoyl-4-O-benzyl-1,2-O-isopropylidene-β-d-fructopyranose (6) was straightforwardly transformed into 5-azido-3-O-benzoyl-4-O-benzyl-5-deoxy-1,2-O-isopropylidene-β-d-fructopyranose (8), after treatment under modified Garegg's conditions followed by reaction of the resulting 3-O-benzoyl-4-O-benzyl-5-deoxy-5-iodo-1,2-O-isopropylidene-α-l-sorbopyranose (7) with lithium azide in DMF. O-debenzoylation at C(3) in 8, followed by oxidation and reduction caused the inversion of the configuration to afford the corresponding β-d-psicopyranose derivative 11 that was transformed into the related 3,4-di-O-benzyl derivative 12. Cleavage of the acetonide of 12 to give 13 followed by O-tert-butyldiphenylsilylation afforded a resolvable mixture of 14 and 15. Compound 14 was transformed into (2R,3R,4S,5R)- (17) and (2R,3R,4S,5S)-3,4-dibenzyloxy-2′,5′-di-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine (18) either by a tandem Staudinger/intramolecular aza-Wittig process and reduction of the resulting intermediate Δ²-pyrroline (16), or only into 18 by a high stereoselective catalytic hydrogenation. When 15 was subjected to the same protocol, (2S,3S,4R,5R)- (21) and (2R,3S,4R,5R)-3,4-dibenzyloxy-2′-O-tert-butyldiphenylsilyl-2,5-bis(hydroxymethyl)pyrrolidine (22) were obtained, respectively.     

5′-Epimeric 3′-deoxy-3′,4′-didehydronucleoside-5′-C-phosphonates: synthesis and structural assignment by NMR and X-ray analyses

Epimeric 5′-(RS) dialkyl 3′-deoxy-3′,4′-didehydro-5′-C-phosphonates were prepared by nucleophilic addition of various dialkyl phosphites to 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes. Whereas direct NMR configuration assignment for the C5′ atom bearing the phosphoryl and hydroxy groups using the J (P,H4′) and J (H5′,H4′) coupling constants is impossible due to the absence of the H4′ atom, successful separation, crystallisation and X-ray crystallographic analysis of a pair of epimeric 5′-C-phosphonates, followed by correlation with a series of NMR parameters, led to efficacious configuration assignment of individual epimers in the mixtures.     

Determination of the absolute configuration of the male aggregation pheromone, 2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol, of the stink bug Erysarcoris lewisi (Distant) as 2Z,6R,1′S,5′S by its synthesis

Lipase-catalyzed asymmetric acetylation of a mixture of (6R,1′S,4′S,5′R)- and (6R,1′R,4′R,5′S)-7′-norsesquisabinen-4′-ol (3) afforded a separable mixture of the recovered former and the acetate of the latter. The recovered alcohol was oxidized to (6R,1′S,5′R)-sesquisabina ketone (2), whose absolute configuration could be assigned by its CD comparison with (1R,5S)-sabina ketone (4). Conversion of (6R,1′S,5′R)-sesquisabina ketone (2) to the bioactive pheromone revealed the stereostructure of the male aggregation pheromone of the stink bug Erysarcoris lewisi (Distant) to be (2Z,6R,1′S,5′S)-2-methyl-6-(4′-methylenebicyclo[3.1.0]hexyl)hept-2-en-1-ol (sesquisabinen-1-ol, 1).     

Enantiopure arenesulfenic acids as intermediates in stereoselective synthesis

New transient arenesulfenic acids were involved in the synthesis of enantiopure 2-arylsulfinyl-1,3-dienes, showing central or axial chirality of the substituted arene residue, apart from the chirality related to the stereogenic sulfur atom. Some of the obtained dienes, that is, (S_a,S_S)- and (S_aR_S)-2-(2′-hydroxy-1,1′-binaphthalen-2-sulfinyl)-3-methyl-1,3-butadienes, were subjected to diastereoselective Diels-Alder cycloadditions with N-methylmaleimide. Removal of the arylsulfoxide auxiliary, in the major adduct, was accomplished by reductive cleavage with Raney nickel.     

Reactions in dry media: reactions of cholesterol and cholestanes on silica bound ferric chloride : Cholestane—diacholestene rearrangement

Reaction of cholesterol with silica bound FeCl₃ resulted in a mixture of 3β-cholesteryl chloride and dicholesteryl ether.5-Cholestene and hydroxy- and halogeno-substituted cholestane derivatives gave on heating at 100° with this reagent a 1:1 mixture of 20-epimeric diacholestenes. The 20(R)-isomer gave with meta-chloroperbenzoic acid 20(R)-α-epoxide, while the 20(S)-gave a mixture of 20(S)-α- and 20(S)-β-epoxides.5α,6β-Dihydrocholestane reacted with the FeCl₃/SiO₂ under milder conditions (50°) to give 6β-hydroxy-20(R)-diacholestene, which was converted to the 20(R)-diacholestene.     

A facile synthesis of 3 or 3,3′-substituted binaphthols and their applications in the asymmetric addition of diethylzinc to aldehydes

By using a direct ortho-lithiation, the ligands (S)-3-methoxymethyl-1,1′-bi-2-naphthol [(S)-1], (S)-3,3′-bis(methoxymethyl)-1,1′-bi-2-naphthol [(S)-2], (S)-3-(quinolin-2-yl)-1,1′-bi-2-naphthol [(S)-3] and (S)-3,3′-bis(quinolin-2-yl)-1,1′-bi-2-naphthol [(S)-4] have been synthesized. (S)-1 and (S)-3 show moderate catalytic properties for the asymmetric diethylzinc addition to aromatic aldehydes.     

A novel titanium tetrachloride-induced rearrangement of an enantiopure 4-naphthyldioxolane. The possible role of titanium in the umpolung of tosyloxy and chlorine

The rearrangement of (2′S,4′R,5′S)-2-(2′,5′-dimethyl-1′,3′-dioxolan-4′-yl)-4,5,7-trimethoxynaphthalen-1-yl 4″-methylbenzenesulfonate with titanium(IV) chloride affords (1R,3S,4R)-10-chloro-6,7,9-trimethoxy-1,3-dimethyl-3,4-dihydro-4-hydroxynaphtho[1,2-c]pyran in good yield. This transformation is characterized by two unusual aromatic substitution reactions in that, in one, tosyloxy is lost and, in the other, aromatic chlorination occurs with titanium(IV) chloride as the source of chlorine.