Synthesis of optically active derivatives of bicyclic chiral diols with C2 symmetry

This paper reports efficient procedures for the preparation of optically active dibromide, diazide, diamine, and unsaturated diesters derived from a chiral bicyclic diol with C₂ symmetry namely (11R,12R)-9,10-dihydro-9,10-ethaneanthracene-11,12-dimethanol 3. Esterification of 3 with saturated and unsaturated carboxylic acids and acids chlorides leads to the corresponding normal-, olefinic- and acetylenic diesters in average yields of 81%. Also more efficient techniques for the preparation of starting diol 3 in higher yields as well as for a very simple separation of DCU (N,N′-dicyclohexylurea) from reactions carried out following the DCC/DMAP method are described.     

Synthesis of optically active 4-substituted 2-cyclohexenones

Recently, Nicolaou and Baran independently synthesized optically active 4-substituted 2-cyclohexenones via an efficient LiOH-mediated intramolecular aldol condensation. Thus far, application of their cyclization approach has been limited to ketoaldehydes where the R-group is branched. It is demonstrated that the LiOH-mediated cyclization, when applied to substrates containing unbranched R-groups, results in significant erosion of optical purity. A mechanistic justification is provided, and a set of neutral, organocatalyzed conditions is identified that enables cyclization with little loss in optical purity.     

Synthesis of optically active bihelicenols

All six stereoisomers of dimethyl 5,5′-dihydroxy-1,1′,12,12′-tetramethyl-[6,6′]bi(benzo[c]phenanthrenyl)-8,8′-dicarboxylate (bihelicenol) were synthesized by the oxidative coupling of methyl 8-hydroxy-1,12-dimethylbenzo[c]phenanthrene-5-carboxylate (helicenol), and their structures were determined by X-ray analysis.     

Synthesis of optically active lipoaminoacids

Conclusions S--(Distearoyl-L-phosphatidyl)--L-alanylglycerol and its R-isomer have been synthesized.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1098–1100, June, 1966.     

Synthesis of optically active penems

A general synthesis for optically active penems is described. Penems undergo a novel thermal isomerisation reaction.     

Synthesis of optically active tetrahydrozerumbone

Tetrahydrozerumbone 2, which has a powerful balmy fragrance, has a stereogenic carbon at C2 and can be easily prepared from zerumbone 1, which is one of the most important materials that displays an NMRDOS character. Reduction of 2 gave two diastereomers 3 and 4; their optically active (>99% ee) alcohols were obtained by lipase-catalyzed stereoselective transesterification of each racemic alcohol. The enantioselectivity of tetrahydrozerumbol does not entirely depend on the hydroxyl position but on the 2-methyl position. Compounds (R)-2 and (S)-2 were obtained by Dess–Martin oxidation of the corresponding alcohols. Interestingly, (R)-2 showed a strong balmy fragrance while (S)-2 had hardly any fragrance.     

Synthesis of optically active hydroxyphosphonates

The reduction of dimenthyl ketophosphonates with sodium borohydride involves asymmetric induction at the α‐carbon atom, resulting in a small excess of the (R)‐enantiomer of the α‐hydroxyphosphonate formed. A higher ee purity was achieved if the reduction of chiral dimenthyl ketophosphonates was carried out by the chiral complex of NaBH₄‐L ‐proline, owing to the double asymmetric induction at the α‐carbon atom. The hydroxyphosphonates obtained were isolated in a diastereomerically pure state and were transformed to the optically active, free hydroxyalkylphosphonic acids. The (R)‐configuration of one of them was proved by X‐ray crystal structure analysis. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:133–139, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20391     

A simple and efficient synthesis of an Asp-Gly dipeptide mimetic

Alkylation of N^α-Boc protected aspartic acid with allyl bromide in the presence of lithium bis(trimethylsilyl)amide (LHMDS) and hexamethylphosphoramide (HMPA) afforded chiral β-allyl substituted aspartic acid in good yields. After deprotection of the N^α-Boc group and reprotection as a trifluoroacetamide, the terminal alkene was oxidized to an aldehyde. The aldehyde was then coupled with l-cysteine through a cascade three-bond formation process to afford aspartic acid-glycine bicyclic dipeptide mimetics.     

Synthesis of bicyclic dipeptide mimetics for the cholecystokinin and opioid receptors

The cholecystokinin C-terminal octapeptide analogue H-Asp-Tyr-D-Phe-Gly-Trp-(N-Me)-Nle-Asp-Phe-NH₂ (SNF 9007) is a potent and selective ligand for both the CCK-B and δ-opioid receptors. To constrain the peptide into the biologically active conformation(s), bicyclic dipeptide mimetics for Nle-Gly and homoPhe-Gly were designed and synthesized from β-substituted aspartic acids. Alkylation of L-aspartic acid using lithium bis(trimethylsilyl)amide (LHMDS) in the presence of hexamethylphosphoramide (HMPA) gave β-substituted aspartic acids, with the major product being the (2S,3R) isomer. Additional isomers of Nle-Gly bicyclic dipeptide mimetic were obtained via the Kazmaier-Claisen rearrangement reaction. The stereochemistries of the bicyclic dipeptide mimetics were assigned by X-ray and NMR.     

Synthesis of an optically active unsaturated silicohydrocarbon containing an asymmetric silicon atom

Summary Starting with vinyltriethoxysilane, we were the first to obtain optically active dextrorotatory and levorotatory isomers of an unsaturated silicohydrocarbon, namely, of vinylphenyl--naphthylsilane.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 387–389, February, 1965     

Synthesis of optically active 5,6,7,8-tetrahydroquinolines

(+)-(R)-5-Methyl- and (+)-(R)-2,5-dimethyl-8-isopropylidene-5,6-dihydro-7H-quinoline, 7 and 11 , were synthesized by reaction of (R)-pulegon morpholino-enamine with acrolein or methyl vinyl ketone. The Michael adducts thus formed were reacted with hydroxylammonium hydrochloride in polar media. Compound 7 was also obtained by thermal rearrangement of the O-allyl ether of pulegone oxime. The selectivity of both synthetic methods were rather poor (30–49%). Isolation of 7 and 11 in the pure state was accomplished by preparative glc.     

光学活性炔丙醇的合成

具有光学活性的炔丙醇是有机合成的重要中间体，其合成方法较多，通常使用 不对称还原、不对称1，2－加成、动力学拆分、2，3σ－重排、消除、还原裂解等 方法合成，其ee值和化学产率均达到了良好的水平，作者将对这类化合物的不对称 合成方法作一总结。