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New chiral nitroenamines 4a,b having ( S )-2- t -butyldimethylsiloxymethylpyrrolidine as an auxiliary were found to be very effective for asymmetric nitroolefination of α-alkyl-γ- and δ-lactones. The enantiomeric excess of the product increased remarkably in the reaction with γ-lactones compared with previous nitroenamines 1a,b . A possible chelation model for the transition state of the asymmetric nitroolefination is discussed.

The structures of nine new diterpenoids from the leaves and stems of Taxus chinensis were elucidated by means of NMR spectroscopy. Some of the new diterpenes were subjected to X-ray crystallographic analysis. Taxchinins D, G, E, H, I, J, K have an 11(15 → 1)-abeotaxane skeleton. Taxchins A and B possess an ordinary taxane skeleton, and belong to the first example of taxoids without an oxygen functionality or the sp 2 -hybridized carbon at C-4. Taxchinins D, E, I, and J exist as a mixture of conformational isomers in solution, whose behavior was investigated by variable-temperature NMR spectra and compared with the conformation obtained from X-ray analysis.

Positively charged methyl-2-amino-6-palmitoyl- d -glycosides (PGLNs), i.e., derivatives of glucose (PGlcN), galactose (PGalN) and mannose (PManN), were synthesized to replace toxic stearylamine (SA) and were incorporated into liposomes. Methyl-6-palmitoyl glycosides (PGLs), namely, derivatives of glucose (PGlc), galactose (PGal) and mannose (PMan), were also synthesized for comparison with PGLN liposomes. PGLN and PGL liposomes newly prepared by extrusion were used to investigate their disposition kinetics in rats. The zeta potentials of liposomes, all of which contain 20 mol% of PGLN and have a diameter of about 200 nm, were about 10 mV in PBS. Those of egg PC/cholesterol and PGLN liposomes had small negative zeta potentials. These PGLN liposomes showed no hemolytic activity and no toxicity in the experimental concentration range. PGLN and PGL liposomes have the same stability as egg PC/cholesterol liposomes in rat serum. PGLNs prolonged the elimination of liposomes from the blood circulation and decreased the hepatic uptake of liposomes, while PGLs showed no effects. It was suggested that the positive charge on PGLNs is one important factor for the prolongation of the residency of liposomes in the blood circulation.

Several chiral 2-nitro-1-sulfinylalkenes were prepared and examined for their utility as dienophiles for asymmetric [4+2] cycloaddition. Trisu- bstituted dienophiles (3-6) undergo distereoselective cycloaddition with cyclopentadiene in the presence of Lewis acids. Even the tetrasubsti- tuted chiral sulfinyl dienophiles (1) and (2) could be coerced into un- dergoing [4+2] cycloaddition to afford the cycloadducts in high yield without concomitant elimination if the reaction was conducted under high pressure. Generally, the Z-sulfinyl dienophiles (1-4) showed higher diastereo- and exdo/exo-selectivity than the E-dienophiles (5) and (6)

Density functional calculations at LSD, NLSD/6-31G*, DZVP2 levels were performed on azoles, azines and their protonated forms. Geometries and dipole moments were well described by both global bases. Energies obtained at NLSD(BP)/DZVP2 level are reasonably comparable with high level ab initio and experimental data. For atomic charges, LSD/6-31G* level gave acceptable results.

The chiral ketone 1 was treated with potassium hydride and a series of alkyl halides in the presence of 18-crown-6 to furnish chiral alkylated ketones 2 in 4873% ee without any external chiral source. These findings contravene the accepted view that chirality at the α-carbon to carbonyl groups is lost in the corresponding enolates because the enolates themselves are achiral. To explain this phenomenon, we propose the novel concept that chirality at the α-carbon to the carbonyl group is memorized as dynamic axial chirality with respect to the C1-C2 bond in the intermediate enolate, and is then regenerated as central chirality in the reaction products (memory of chirality). This mechanism was supported by trapping the enolate as a methyl enol ether 11 of 65% ee. The present concept was successfully applied to the development of the asymmetric α-alkylation reactions of α-amino acids. Thus, phenylalanine derivative 22 was found to undergo asymmetric α-alkylation in up to 88% ee when treated with lithium 2, 2, 6, 6-tetramethylpiperidide followed by alkyl halides.

α-Allylation of 3 took place upon treatment with KHMDS followed by allylic halides in 82–87% ee in the absence of external chiral sources. A chiral nonracemic enolate with intramolecular aggregation ( D ) is expected to be an intermediate.

An optically active spiropyran 1 with a binaphthol moiety as a chiral source was synthesized. The colored merocyanine form of (R)-1 obtained by the UV irradiation remained in the presence of D-amino acids longer than with L-amino acids. Chirality 14:713–715, 2002. © 2002 Wiley-Liss, Inc.

Five new diterpenoids, taxchinins A {3}, B{4}, and C{5}, 19-hydroxy-7-epibaccatin III {6}, and 10-deacetyl-10-oxobaccatin V {7}, have been isolated from the needles and stems of Taxus chinensis together with twelve known compounds including taxol {1}. These structures were elucidated and identified by spectroscopic techniques. A single X-ray crystallographic analysis of taxchinin A {3} determined its unique 51716-membered ring system. Taxchinins B {4} and C {5} were shown to have the same ring system

An enantiodivergent method for preparation of threo β-amino alcohols and threo 1,2-diamines has been developed starting with a chiral aziridine 1. Unusual amino acid derivatives 3 and 5, which are key synthetic intermediates for bestatin and the related peptides, have been prepared.

A chiral phosphonoacetate 2 differentiates the enantiotopic carbonyl groups in an α-diketone 5 to afford the Z-olefin 6 in high yield and ee. The absolute stereochemistry of 6 was determined by X-ray analysis of 8 derived from 6.

A new reagent system (silver nitrite-iodine) was developed for demonothioacetalization and dedithioacetalization reactions. The reaction using this reagent afforded the parent carbonyl compound in excellent yield under mild conditions.

Asymmetric protonation utilizing hydrochlorides of chiral piperazine derivatives has been investigated. Protonation of the lithium enolate derived from 1-acetoxy-2-benzylcyclohexene with (2 R , 5 R )-2,5-diphenylpiperazine monohydrochloride ( 2 ) resulted in a formation of ( S )-2-benzylcyclohexanone in 70% ee. The enantioface-differrentiating protonation with the salts of related chiral piperazine derivatives are also discussed.

[reaction: see text] A total synthesis of spirotryprostatin B was accomplished via asymmetric nitroolefination as a key step.

[structure: see text] A hybrid molecule 1 consisting of phenolphthalein and two crown ether moieties can be used to discriminate the length of linear triamines strictly by color development. The purple color is developed most deeply at -10 degrees C and fades with either an increase or decrease in temperature.

Cycloenantiomeric hexahomooxacalix[3]arenes with different substituents on the three upper rims were synthesized for the first time by fixing their conformation into a cone. A cycloenantiomeric hexahomooxacalix[3]arene 6 was resolved into both enantiomeric forms and chiroptically characterized. Preliminary 1H-NMR studies indicated that the optically resolved cycloenantiomer 6 could discriminate the enantiomers of hydrochloride of phenylalanine ethyl ester.

Nitroalkenes were prepared by the substitution reaction of β-nitrovinyl sulfides and sulfoxides [1-ethylsulfinyl-2-nitrocyclohex-1-ene, -cyclohept-1-ene and (E)-2-ethylsulfinyl-1-nitroprop-1-ene] with a variety of carbon nucleophiles (i.e. alkylmetal reagents and enolates of carbonyl compounds), via an addition-elimination sequence. The sulfoxide as a leaving group was suitable for the reaction with an enolate of carbonyl compounds

The Diels-Alder reaction of chiral 2-alkylsulfinyl-1-nitroalkene 1 and Danishefsky's diene (2) afforded adducts 3 and 4 in good chemical yield with a high enantiomeric excess, while diastereomeric nitroalkene 7 gave 8 and 9 , enantiomeric to 3 and 4 , respectively

The reaction of β-nitro-α,β-unsaturated sulfoxide 7 with δ-lactam enolates 11 – 15 afforded 20 – 24, respectively, in good chemical yields with high enantiomeric excesses.

Highly diastereoselective methylation of binaphthyl esters of arylacetic acids and its application to the syntheses of antiinflammatory drugs, ( S )- suprofen and ( S )-naproxen.

Asymmetric dihydroxylation of a variety of olfins has been achieved by employing the chiral ligands of N,N′-dialkyl bispiperazines having linker arm of two carbons in excellent to good enantioselectivity.

Using the high pressure technique, asymmetric Diels-Alder reaction utilizing chiral 2-nitro-1-sulfinylolefins and dienes proceeded smoothly to give highly functionalized cyclohexene derivatives with satisfactory chemical yield and high diastereomeric excess.

Organometallic reagents undergo a 1,4-addition onto the chiral binaphthyl ester of α,β-unsaturated carboxylic acid followed by the formal 1,2-addition to yield optically active ketones directly.

A concise synthesis, from the chiral nitroalkene 1a, of (+)-podocarpic acid is described. This was transformed into (+)-lambertic acid via a chromium complex.

An enantiodivergent method for preparation of threo β-amino alcohols and threo 1,2-diamines has been developed starting with a chiral aziridine 1. Unusual amino acid derivatives 3 and 5, which are key synthetic intermediates for bestatin and the related peptides, have been prepared.

Asymmetric protonation utilizing hydrochlorides of chiral piperazine derivatives has been investigated. Protonation of the lithium enolate derived from 1-acetoxy-2-benzylcyclohexene with (2 R , 5 R )-2,5-diphenylpiperazine monohydrochloride ( 2 ) resulted in a formation of ( S )-2-benzylcyclohexanone in 70% ee. The enantioface-differrentiating protonation with the salts of related chiral piperazine derivatives are also discussed.

A new reagent system (silver nitrite-iodine) was developed for demonothioacetalization and dedithioacetalization reactions. The reaction using this reagent afforded the parent carbonyl compound in excellent yield under mild conditions.

The reaction of 4-lithio-2,2-dimethyl-1,3-oxathiane 3,3-dioxide with various electrophiles is presented. Acylation of the anion provided labile 4-acyl-2,2-dimethyl-1,3-oxathiane 3,3-dioxides which underwent desulfonation with silica gel to produce γ-hydroxy ketones with three carbon unit elongation. Thus, 4-lithio-2,2-dimethyl-1,3-oxathiane 3,3-dioxide was shown to be a useful synthetic equivalent of a γ-hydroxypropyl anion. Methyl esters proved to be the best acylating agents in this reaction

A chiral phosphonoacetate 2 differentiates the enantiotopic carbonyl groups in an α-diketone 5 to afford the Z-olefin 6 in high yield and ee. The absolute stereochemistry of 6 was determined by X-ray analysis of 8 derived from 6.

The Diels-Alder reaction of 5-iodo- (1a) and 5-ethylsulfonyl-2-methyl-3(2H)-pyridazinone (1b) with 2,3-dimethyl- 1,3-butadiene afforded phthalazinone (3) and dihydrophthalazinone (2) as isolable products, respectively. The cycloadditions are well interpreted by the theoretical considerations based on the calculated AM1 data

Several chiral 2-nitro-1-sulfinylalkenes were prepared and examined for their utility as dienophiles for asymmetric [4+2] cycloaddition. Trisu- bstituted dienophiles (3-6) undergo distereoselective cycloaddition with cyclopentadiene in the presence of Lewis acids. Even the tetrasubsti- tuted chiral sulfinyl dienophiles (1) and (2) could be coerced into un- dergoing [4+2] cycloaddition to afford the cycloadducts in high yield without concomitant elimination if the reaction was conducted under high pressure. Generally, the Z-sulfinyl dienophiles (1-4) showed higher diastereo- and exdo/exo-selectivity than the E-dienophiles (5) and (6)