Enantioselective Synthesis of Key Intermediates in a Novel Approach towards the Iboga‐Alkaloid Family

Significant improvements in the realm of a recently disclosed, novel synthetic concept towards the Iboga alkaloid family are presented. The key step for the construction of the bicyclic aliphatic core consists of an intramolecular nitrone? olefin 1,3‐dipolar cycloaddition reaction of a 1 : 1 mixture 15 / 16 yielding the two diastereoisomeric tricyclic isoxazolidine derivatives 17 and 18 . The required nitrones were prepared from the readily available (S)‐hydroxylactone 6 in twelve steps with an overall yield of 15% (average: 83.5% per step). The relative configuration of the minor isomer was deduced unambiguously by single‐crystal X‐ray analysis of the derived tricyclic carbamate 21 . As four out of five asymmetric centers in the pair 17 / 18 have opposite configuration, destruction of the one possessing the same absolute configuration transforms the original set of diastereoisomers into a pair of enantiomers. We verified this contention by oxidizing the two alcohols 20 and 22 to yield the two antipodal forms of ketone 23 . The absence of significant amounts of by‐product and the high reproducibility of the crucial cycloaddition reaction represent marked improvements over our earlier attempts. In addition, the new route, which starts from L ‐glutamate, should provide access to both naturally occurring antipodal series of the targeted alkaloid class.     

盐酸普拉克索关键中间体的合成

以1,4-二氧杂螺[4.5]癸-8-酮(2)为起始原料,经三甲基硅烯醚化、碘代反应、酸化后所得的产物,与硫脲发生环合、水解后制得2-氨基-6-氧代-4,5,6,7-氢苯并[1,2-d]噻唑(5,经氨化还原反应合成了2,6-二氨基-4,5,6,7-四氢苯并[1,2-d]噻唑(6)。5和6两种关键中间体的总收率分别为86%和71%,其结构经MS、¹H NMR和¹³C NMR确证,探索了合成盐酸普拉克索的两种关键中间体方法和工艺的影响因素。     

醋酸乌利司他关键中间体的合成工艺

3,20-二(亚乙二氧基)-17-α-羟基-19-去甲孕甾-5(10),9(11)-二烯为合成选择性孕酮受体调节剂醋酸乌利司他(Ulipristal Acetate)的关键中间体。以环-3-(1,2-亚乙基缩醛)-雌甾-5(10), 9(11)-二烯-3,17-二酮(UPA-O)为原料,经亲核取代、亲核加成、Mislow-Evans重排、醚键断裂、烯醇式互变、缩酮保护等反应,制备该关键中间体。对合成路线中反应条件进行工艺优化,总收率74.8%。     

Towards Total Synthesis of Forskolin I. The Synthesis of Fragment Intermediates A and B

Methods for synthesis of two crucial intermediate A and B starting with 2,4,4-trimethyl-2-cyclo-hexenone 1 and 2,3-dibromofuran 9 are disclosed.     

Dianions of Unsaturated Carboxylic Acids in Synthesis. Synthesis of Juvocimene I

Juvocimene I is prepared by a non ambiguous synthesis based on the regioselective alkylation of 4-methylhexa-2,4-dienoic acid, and Wittig olefination of the aldehyde corresponding to the alkylated acid.     

Synthesis of Pharmaceutical Intermediates by Toluene Benzylation over Heteropoly Acids on Different Support

Selective formation of pharmaceutical intermediates like diphenylmethane, dimethyl- diphenylmethane, benzyl toluene and benzoic acid by liquid phase, toluene benzylation with benzyl chloride as a benzylating agent, was systematically studied over plane clay (K-10, montmorillonite), plane H-Beta, plane MFI structured titanosilicate (TS-1) and heteropoly acids [HPA, namely dodeca-tungstophosphoric acid [H3PO4.12WO3.xH2O] (TPA), dodeca-molybdo phosphoric acid ammonium salt hydrate [H12Mo12N3O40P aq] (DMAA), sodium tungstate hydrated purified [Na12WO4.2H2O] (STH)] supported on clay, H-beta and TS-1. The 20%TPA/Clay, 30%TPA/H-Beta and 30%TPA/TS-l, were observed to be the best catalyst samples over plane clay, plane H-Beta and plane TS-1. The catalyst samples are compared with respect to benzyl chloride conversion and selectivities for diphenylmethane, dimethyl-diphenylmethane, benzyl toluene and benzoic acid. The reaction follows the pseudo-first order rate power law model. The apparent rate constants are calculated and compared with the reported ones.     

Synthesis of Three Organo-Bridged Coupled Key Intermediates in the Stepwise Coupling Polymerization

Three new organo-bridged coupled compounds, as the key intermediates in a new route, so-called Stepwise Coupling Polymerization, were synthesized in high yields by preamminolysis reaction.     

Bioinspired Synthesis of Pulvinic Acids Including Xerocomic Acid and Fluorescence Properties of Bis-lactone Intermediates

A set of representative pulvinic acids were synthesised using a bioinspired strategy. Terphenyl-quinones (polyporic acid scaffold) were prepared via sequential Suzuki-Miyaura couplings allowing access to unsymmetrically substituted derivatives in a one-pot protocol. Subjected to the action of acetic anhydride and DMSO, quinones were converted into bis-lactone intermediates. Methanolysis and deprotection achieved the total syntheses of the corresponding pulvinic acids. Following this general strategy, symmetrical pulvinic, atromentic, variegatic acids and unsymmetrical congener pinastric, iso-pinastric, xerocomic and iso-xerocomic acids were prepared in fair yields. Fluorescence properties were observed for the bis-lactone intermediates and, as a complement to this synthetic work, optical properties were measured, and fluorescence quantum yields were determined for the bis-lactone pigments.     

Synthesis and Asymmetric Enantioselective Addition of Chiral Polybinaphthyl and Polybinaphthol I.igands

Four chiral polymers P-1, P-2, P-3 and P-4 were synthesized by the polymerization of （S）-2,2＇-dioctoxy-1,1＇- binaphthyl-6,6＇-boronic acid （S-M-3） with （S）-6,6＇-dibromo-1,1＇-binaphthol （S-M-1）, （R）-6,6＇-dibromo-1,1＇- binaphthol （R-M-1）, （S）-3,3＇-diiodo-1,1＇-binaphthol （S-M-2） and （R）-3,3＇-diiodo-1,1＇-binaphthol （R-M-2） under Pd-catalyzed Suzuki reaction, respectively. All four polymers can show good solubility in some common solvents due to the nonplanarity of the polymers in the main chain backbone and flexible alkyl groups in the side chain. The analysis results indicate that specific rotation and circular dichroism （CD） spectral signals of the alternative S-S chiral polymers P-1 and P-3 are larger than those of S-R chiral polymers P-2 and P-4, but their UV-Vis and fluorescence spectra are almost similar. The results of asymmetric enantioselectivity of four polymers for diethylzinc addition to benzaldehyde indicate that catalytically active center is （R） or （S）-1, 1＇-binaphthol moieties.     

常山碱及其类似物关键中间体的合成研究进展

综述了常山碱(2)及其类似物常山酮(3)的合成研究现状,从哌啶环构建策略包括吡啶环还原法、分子内亲核进攻法、RCM反应(关环复分解反应)及扩环反应法等,重点介绍了近年来2和3的关键中间体3-羟基哌啶衍生物的合成研究进展,并对各合成路线的优缺点进行了简要评述。参考文献24篇。     

An Enantioselective Chemoenzymatic Synthesis of the Four 1-Amino 2-Methylcyclopropane Carboxylic Acids

Racemic 2-methylcyclopropane dicarboxylic acid dimethyl ester undergoes selective enzymatic reactions to give enantiomerically pure monocarboxylic acids which by classical organic chemistry lead to the four 1-amino 2-methyl cycloproane carboxylic acids.     

Keteniminium Salts as Key Intermediates for the Efficient Synthesis of 3-Amino-Indoles and -Benzofurans

Herein, we describe a high yielding approach towards the synthesis of 3-amino-indoles and -benzofurans through 6π-electrocyclization. This was made possible by taking advantage of the high reactivity of keteniminium salts, formed in-situ by treating with triflic anhydride and 2-fluoropyridine amides bearing at the α-position either an aniline or a phenoxy moiety. These mild conditions, on top of furnishing rapidly the 3-aminobenzoheteroles, allow the tolerance of various functional groups. Control experiments were carried out to highlight that the keteniminium is, indeed, in most cases, the reactive intermediate and conformational preferences of such species were investigated through a DFT study.