A novel highly stereoselective synthesis of 2,3-disubstituted 3H-quinazoline-4-one derivatives

[structure: see text]. An efficient three-step synthesis of chiral 3H-quinazoline-4-one derivatives from commercial materials is disclosed. The Mumm reaction of imidoyl chloride with alpha-amino acids followed by reductive cyclization affords enantiomerically pure (ee >93%) quinazoline-4-ones in good overall yield. A comparison with existing approaches indicates that this method is superior for hindered substrates.     

A novel and highly stereoselective synthesis of 2-substituted perhydrofuro[2,3-b]pyran derivatives

An effective and facile method for the synthesis of 2-substituted perhydrofuro[2,3-b]pyran derivatives is described. The cyclization of 2-C-aldehydo-2-deoxy-D-thioglucoside in the presence of N-iodosuccinimide (NIS) is highly stereoselective. 2-Substituted cyclization products were obtained in good to excellent yields.     

A highly stereoselective total synthesis of (±)-isoalantolactone

(±)-Isoalantolactone (1) has been synthesized by a highly stereoselective route from the versatile bicyclic ketone, trans-5-methylene-9-methyl-2-decalone 2. Three major points in the synthesis involve (a) introduction of the acetic acid side chain; (b) stereoselective reduction of the ketone function yielding cis-lactone 6; and (c) introduction of the α-methylene group onto the butyrolactone ring.     

A highly stereoselective synthesis of (±)-dihydrofumariline-1

Stereoselective sodium borohydride reduction of the 8,14-cycloberbine (9) derived from the protoberberine (7), followed by reductive cleavage of C₈-N bond of the resulting 13-hydroxy-8, 14-cycloberbine (10) with sodium cyanoborohydride afforded the spirobenzylisoquinoline (12), N-methylation of which via the oxazolidine (13) provided (±)-dihydrofumariline-l (1).     

First highly stereoselective synthesis of anti-alpha-trifluoromethyl-beta-amino acid derivatives

The Reformatsky-type reaction of 2-bromo-3,3,3-trifluoropropanoic imide with various types of imines, in the presence of ZnBr2 as a Lewis acid in THF at 0 degrees C for 3 h, gave the corresponding alpha-trifluoromethyl-beta-amino acid derivatives in a highly anti-selective manner.     

A stereoselective synthesis of (+)-L-733,060 from ethyl (R)-(+)-2,3-epoxypropanoate

An asymmetric synthesis of neurokinin substance P receptor antagonist (+)-L-733,060 starting from enantiomerically pure ethyl (R)-(+)-2,3-epoxypropanoate (ethyl glycidate) is described. The synthesis relies on a diastereoselective reductive amination, regioselective intramolecular epoxide opening, and in situ cyclization as the key steps.     

A new strategy for the stereoselective synthesis of 2,3-dideoxy-3-fluoro-D-ribofuranose derivatives

The important intermediate for syntheses of various anti-HIV nucleoside analogues, methyl 2,3-dideoxy-3-fluoro-6-O-(p-methylbenzoyl)-a-D-ribofuranoside, was synthesized starting from 2-deoxy-D-ribose in 5 steps with an overall yield of 24%. This strategy can be also used for synthesizing other analogues with various substitutions at 3-C position.     

A new synthesis of α,α-disubstituted carbonyl compounds from carbonyl compounds with one-carbon homologation

Lithium α-sulfinyl carbanions of 1-chloroalkyl p-tolyl sulfoxides were reacted with carbonyl compounds to afford adducts in high to quantitative yields. The adducts were treated with t-BuMgCl or LDA to give magnesium or lithium alkoxides, which were treated with i-PrMgCl or t-BuLi to afford the enolate with one-carbon elongation through β-oxido carbenoids. The enolate intermediates were found to be able to be trapped with electrophiles to give α,α-disubstituted carbonyl compounds in moderate to good yields. As a whole, this procedure offers a new and good method for synthesis of α,α-disubstituted carbonyl compounds from carbonyl compounds with one-carbon homologation in only two synthetic steps.     

A new and highly stereoselective synthesis of polyhydroxyindolizidines from 4-octulose derivatives

(1S,2S,6R,7R,8R,8aR)-1,2,6,7,8-Pentahydroxyindolizidine 12 and (1R,6R,7R,8R,8aR)-1,6,7,8-tetrahydroxyindolizidine (1,6-diepicastanospermine, 24) have been stereoselectively synthesized from the important key intermediates l,4-dideoxy-1,4-imino-d-erythro-l-altro-octitol 7 and 1,2,4-trideoxy-1,4-imino-d-glycero-d-talo-octitol 20 in three steps. Compounds 7 and 20 were readily obtained from 2,3:4,5:6,7-tri-O-isopropylidene-β-d-glycero-d-galacto-oct-4-ulo-4,8-pyranose 1 and 2-deoxy-4,5:6,7-di-O-isopropylidene-β-d-manno-oct-4-ulo-4,8-pyranose 13 in four steps, respectively.     

A highly convergent synthesis of mexiprestil: 16(R) 16-methoxy 16-methyl PGE1 methyl ester

The synthesis of optically pure mexiprostil, a PGE₁ analogue, via the three component coupling process, e.g. Michael addition of the appropriate ω-side chain onto enantiomerically pure, protected (R)-4-hydroxy-cyclopentenone, followed by in situ trapping with the a-side chain, is described.     

A highly stereoselective asymmetric synthesis of (--)-lobeline and (--)-sedamine

A highly stereoselective asymmetric synthesis of (--)-sedamine and (--)-lobeline is described from benzaldehyde in 16 and 17 steps with an overall yield of 20% and 14%, respectively. The key intermediate syn-3,4-epoxyalcohol was prepared in a highly diastereomeric fashion (>99% ee, dr) and served as a common intermediate for both alkaloids.     

A stereoselective synthesis of 3(R)-hydroxy-2(S)-ornithine

(2S,3R) Threo-3-hydroxy-ornithine has been synthesized efficiently using a highly stereoselective iodocyclocarbamation of the chiral Z-olefin 7 prepared from D-serine.     

A highly stereoselective synthesis of (E)-1-substituted-1,3-dienes

(E)-1-substituted-1,3-dienes are obtained with high stereoselectivity by the thermal extrusion of SO₂ from 2-substituted-2,5-dihydrothiophene-1,1-dioxides generated by a retro Diels-Alder reaction. An application to the synthesis of (E)-9,11-dodecadien- 1-yl acetate, a sex pheromone of the red-bollworm moth is described.     

A facile and efficient stereoselective synthesis of highly functionalised trisubstituted alkene derivatives of ferrocenealdehyde

The reaction of the Baylis–Hillman adduct 2 of ferrocenealdehyde with various oxygen and carbon nucleophiles in the presence of montmorillonite K10 clay catalyst furnished highly functionalised trisubstituted alkene derivatives of ferrocenealdehyde in excellent yield. Synthetic use of one of products 7 has been demonstrated with the synthesis of a 1,3-diyne ether derivative of ferrocene 16 via an Eglinton coupling reaction.     

A practical stereoselective synthesis of (2R,3S)-alloisoleucine

An efficient asymmetric Strecker synthesis of the unnatural α-amino acid, d-alloisoleucine (3), from commercially available and inexpensive (S)-2-methyl-1-butanol (4) was accomplished in four steps.     

A short and highly stereoselective synthesis of α-(2-aminothiazolyl)-C-nucleosides

A short route to novel α-(2-aminothiazolyl)-C-nucleosides has been developed. The key step was the high diastereoselective reduction of the hemiacetal intermediates using L-Selectride, which afforded the corresponding R-diols in quantitative yields. These diols were converted, after C4-C1 ring closure and protecting groups cleavage, to their corresponding free α-C-nucleosides.