Stereoselective synthesis of 3-(ω-hydroxyalkyl)-2-pyrrolidinones from α-alkylidenelactones and nitromethane

Enantiopure 3-(ω-hydroxyalkyl)-2-pyrrolidinones 7 and 9 were synthesised by Michael-addition of nitromethane to chiral α-alkylidenelactones 1 followed by reduction of the resulting 3-(β-nitroalkyl)-lactones and ring transformation of the intermediate 3-(β-aminoalkyl)-lactones. In an analogous manner the naturally occurring costuslactone 10 was transformed into the butyrolactam 12.     

Scope and limitations of the photooxidations of 2-(α-hydroxyalkyl)furans: synthesis of 2-hydroxy-exo-brevicomin

Photooxygenation of 2-(α-hydroxyalkyl)furans at 5 °C in MeOH followed by in situ reduction affords, in one synthetic operation, 6-hydroxy-3(2H)-pyranones and/or 5-hydroxy-2(5H)-furanones. The relative ratio of the final products is highly dependent on the substitution of the starting furan substrate. Photooxygenation of 2-(α,β-dihydroxyalkyl)furans followed by in situ reduction and ketalization with acid rapidly provides the 6,8-dioxabicyclo[3.2.1]oct-3-en-2-one framework. This new methodology was successfully applied to the synthesis of 2-hydroxy-exo-brevicomin.     

Stereoselective synthesis of triterpene 2-deoxy-α-d-lyxo-hexopyranosides

2-Deoxy-α-d-lyxo-hexopyranosides of 18β-glycyrrhetic acid, its 11-deoxo derivative and allobetulin were synthesized by glycosylation of oleonane-type triterpene alcohols withd-galactal acetate in the presence ofN-iodosuccinimide followed by deiodination and deprotection. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 596–600. March, 1997.     

Stereoselective synthesis of 2-deoxy-α-d-arabino-hexopyranosides of triterpene alcohols

2-Deoxy-2-iodo--d-mannopyranosides of triterpene alcohols of the oleanane series were synthesized inca. 60% yields by glycosylation with readily accessibled-glucal triacetate in the presence ofN-iodosuccinimide as the promotor. Their deiodination by catalytic hydrogenation followed by deacetylation yielded 2-deoxy--d-arabino-hexopyranosides of glycyrrhetic acid derivatives and allobetulin.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2340–2346, September, 1996.     

Stereoselective synthesis of β-(hydroxymethylaryl/alkyl)-α-methylene-γ-butyrolactones

Zinc or a chromium(II) source with 3-(bromomethyl)furan-2(5H)-one (3) and an aldehyde gives β-(hydroxymethylaryl/alkyl)-α-methylene-γ-butyrolactones 5 in good yields and high diastereoselectivities. The methodology is demonstrated in concise syntheses of (±)-hydroxymatairesinol (8) and (±)-methylenolactocin (10) by subsequent arylboronate conjugate addition and translactonization, respectively.     

Stereoselective total synthesis of (±)-peribysin E

Radical cyclization of iodoketone 3 afforded cis-hydrindanone 8. Compound 8 was converted into key intermediate 5 via conventional transformations. Annulation of a spiro-lactal unit to 5 was pursued with three different approaches. In the first approach, radical cyclization of propargyl ester 17 provided spiro-lactone 18 with an undesired stereochemistry. Attempts to invert the stereochemistry at the spiro-center via retro-aldol and aldol condensation of compound 20 failed. In the second approach, key intermediate 5 was transformed into 23. Acylation of compound 23 gave 24 as a single diastereomer with the desired stereochemistry but in low yield. NBS bromination of 24 followed by lactone formation gave 26 in low yield. Alternatively, allylic oxidation of 24 with SeO(2) followed by lactonization gave 26 also in low yield. Finally, a third approach employing a semipinacol-type rearrangement of epoxy-alcohol 33 gave aldehyde 34 with the desired stereochemistry. Treatment of compound 34 with HCl in MeOH effected spiro-lactal formation and provided (±)-peribysin E. The overall yield of our synthesis is 3.2% from 2-methylcyclohenen-1-one.     

Stereoselective synthesis of s-(2-deoxy-α-D-glycosyl)- phosphorodithioates1 and of their (2R)-2-deoxy-2-deuterio- analogues. Novel route to C-2 d

Addition of 0,0-dialkylphosphorodithioic acids to fully protected 1,2-unsaturated hexo- and pentopyranoses gives S-(2-deoxy-glycosyl)-phosphorodithioates in quantitative yield and high stereoselectivity with respect to the α-isomer. The stereochemistry of this reaction is “cis” as demonstrated by the addition of deuterated 0,0-dialkylphosphorodithioic acids to 3,4,6-tri-O-acetyl-D-glucal which gives exclusively the α-dithiophosphates of (2R)-2-deoxy-2-deuterio-D-arabinohexopyranose. This result provides an efficient and fully stereoselective method of labeling of the deoxy function in 2-deoxy monosaccharides and their glycosylic derivatives.     

Stereoselective synthesis of syn-α-methyl-β-hydroxy esters

Boron enolates of an ethyl ketone structurally related to erythrulose react with achiral aldehydes in a highly stereoselective fashion to yield 1,2-syn/1,3-syn stereoisomers. Oxidative cleavage of the aldol adducts yields enantiopure O-formylated syn-α-methyl-β-hydroxy esters, easily cleaved to the corresponding hydroxyl-free compounds. The aforementioned ketone behaves therefore as a chiral propionate enolate equivalent.     

Stereoselective synthesis of α,α′-diamino-dicarboxylic acids. Part 2

Enantiomerically pure α,α′-diamino-dicarboxylic acids (R,R)-4, (S,S)-5 and (S,S)-7 have been synthesized starting from the glycine-derived chiral synthon (S,S)-1.     

α-hydroaxyalkyl(benzyl)furozans and α-hydroxyalkyl(benzyl)furoxans synthesis and reactivity

A general and simple preparative method for the synthesis of -hydroxyalky(benzyl)furazan and -furoxan derivatives is proposed, The method involves reduction of acyl or ethoxycarbonyl substituents in these heterocyclic compounds with NaBH₄ in ethanol. Based on the alcohols thus prepared, a number of previously unknown functional derivatives (-nitroxyalkyl--haloalkyl-, and -azidoalkylfurazans and -furoxans) have been synthesized.Translated fromInvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7. pp, 1782–1788, July, 1996.     

Stereoselective total synthesis of (-)-spirofungin A by utilising hydrogen-bond controlled spiroketalisation

The stereoselective total synthesis of the spiroketal containing Streptomyces metabolite (?)‐spirofungin A ( 1 ) is described. A key step involved a spiroketalisation controlled by an intramolecular H‐bond which favoured the desired spiroketal 4 (13:1 ratio). The presence of the intramolecular H‐bond in 4 is possibly due to a 1,5‐alkyne–oxygen interaction. Other key steps include an efficient cross‐metathesis to form the spiroketal precursor, a tin mediated syn‐aldol reaction and a Stille cross‐coupling reaction to create the C22? C23 bond. A final Wittig extension followed by deprotection gave (?)‐spirofungin A ( 1 ).     

Stereoselective,nonracemic synthesis of ω-borono-α-amino acids

ω-Unsaturated α-amino acids are synthesized through condensation of allyl and propargyl bromides or of 9-bromoundecene with a Ni(II) complex of the Schiff base derived from glycine and BPB. Hydroboration with Ipc₂BH followed by oxidation with acetaldehyde affords enantiomerically pure ω-borono-α-aminocarboxylic acids.     

Stereoselective synthesis of (−)-cytoxazone

A novel stereoselective synthesis of (−)-cytoxazone 1 was achieved via addition of p-methoxyphenylmagnesium bromide to the benzylimine derived from (S)-2,3-O-isopropylidene glyceraldehyde followed by one-step regioselective cyclization of N-Boc amino diol 7.     

Stereoselective synthesis of (±)-erythro- and threo-γ-hydroxynorvaline

Both diastereomers of racemic γ-hydroxynorvaline were prepared from 4-penten-2-ol to illustrate a new general method for stereoselective synthesis of either erythro- or threo-1,3-amino alcohol systems from a single precursor.     

Synthesis of 2-(2-Thienyl)benzimidazoles by the Reaction of 2-(Mercaptomethyl)benzimidazole With β-Electrophilic Esters

New 2-(2-di- and tetrahydrothienyl)benzimidazole compounds were prepared by the ring closure reactions of 2-(mercaptomethyl)benzimidazole^1,2 (1) and α,β-unsaturated compounds activated with electron-withdrawing groups.     

A stereospecific synthesis of optically pure (-)-α-multistriatin

An efficient stereo- and enantiospecific synthesis of (-) -α-multistriatin from (L)- malic acid is described. The key steps of this synthesis are the stereoselective alkylation of the hydroxylactone $\text{5}$ and the acid equilibration of the esters $\text{9}$ and $\text{10}$.