A Concise Flow Synthesis of Efavirenz

Efavirenz is an essential medicine for the treatment of HIV, which is still inaccessible to millions of people worldwide. A novel, semi‐continuous process provides rac‐Efavirenz with an overall yield of 45 %. This streamlined proof‐of‐principle synthesis relies on the efficient copper‐catalyzed formation of an aryl isocyanate and a subsequent intramolecular cyclization to install the carbamate core of Efavirenz in one step. The three‐step method represents the shortest synthesis of this life‐saving drug to date.     

Synthesis of Cyclodextrin and Sugar-Based Oligomers for the Efavirenz Drug Delivery

Summary: In the present work water-soluble lactose based oligomers of β-cyclodextrin were synthesized by a simple and efficient condensation polymerization process. Proposed water-soluble β-cyclodextrin oligomers were prepared by controlled reaction between β-cyclodextrin and a triazine linker and purification by an ultrafiltration process. Similarly, lactose based β-cyclodextrin oligomers were synthesized for enhanced water solubility. The physical and chemical properties of the synthesized polymers were characterized by FT-IR and ¹H NMR spectroscopy, XRD analysis, thermogravimetric analysis (TGA) and aqueous solubility determination.. Molecular weights of these β-cyclodextrin based oligomers were measured by ESI technique. These β-cyclodextrin based water-soluble oligomers polymers were used as supramolecular carriers for efavirenz (an anti HIV drug), improving the inclusion property and aqueous solubility properties of this drug. These synthesized oligomers were found to improve stability and aqueous solubility of efavirenz on their (1:1) inclusion complex through phase solubility and dissolution studies. Reduced cytotoxicity than the parent β-CD was observed in hemolysis test.     

Sulfimide-mediated Asymmetric Synthesis

Enantiomerically enriched sulfimides are used to prepare enantiomerically enriched epoxides, aziridines and substituted tetrahydro-furans and -pyrans. A new ‘asymmetric sulfimidation’ procedure is described.     

奈必洛尔的不对称合成

首先合成4-氟-2-(5-羟基戊烷基-3-烯)-苯酚(2), 再经Sharpless不对称环氧化等反应分别得到2-氨基-1-[6-氟- (2S)-3,4-二氢-2H-2-苯并吡喃]-(1R)-1-乙醇(6)和6-氟-2-[(2R)-2-环氧乙烷基]-(2R)-3,4-二氢苯并吡喃(10). 最后, 6和10发生亲核开环反应即得到目标产物奈比洛尔. 整个合成路线简单易行, 并在原有文献的基础上有较大改进, 使收率大大提高, 总收率由文献的2.1%提高到14.1%.     

Asymmetric Synthesis of Anisodine

Anisodine was synthesized from 3α-hydroxy-6β-acetyltropine in 11 steps. Laevorotary isomer of anisodine was prepared from the asymmetric dihydroxylation of compound 10 via the osmium catalyzed process employing p-chlorobenzoyl dihydroquinidine as the chiral ligands.     

左旋薄荷醇的不对称合成

以4-羟基-2-丁酮和异丙叉丙酮为起始原料,经羟醛缩合、不对称氢化、羰基还原、钌催化氢化等4步反应制得左旋薄荷醇。总产率为33%,非对映体过量de值达到93%。详细探讨了铜催化剂及其用量、手性配体的选择、反应溶剂和时间等因素对胡薄荷烯酮不对称氢化反应的影响。中间体及目标化合物均通过了¹H NMR、¹³C NMR和HRMS等技术手段的分析测定及结构表征。     

聚合物支载的不对称有机合成

聚合物支载的不对称有机合成比相应的小分子合成体系有独特的优越性。本文综述了近10年来取得了较大进展的聚合物支载的不对称有机合成体系。     

An Asymmetric Synthesis of Isoindolinones

Recently, the results from this laboratory showed that the reductive alkylation of protected (S)-malimide could be achieved in a high regio- and diastereoselective manner. The substituted 2-pyrrolidinones thus formed are versatile chiral building blocks which can be used in the asymmetric synthesis of pyrrolidines^[1,2],2-pyrrolidinones^[3,4] and β-hydroxy-γ-amino acids^[5,6]. As an extension of this work, and in combination with the current interest in the synthesis of isoindolin-1-ones, a study on the asymmetric reductive alkylation of phthalimide derived from (R)-phenylglycinol was undertaken.     

Asymmetric Formal Synthesis of Azadirachtin

An asymmetric formal synthesis of azadirachtin, a potent insect antifeedant, was accomplished in 30 steps to Ley’s synthetic intermediate (longest linear sequence). The synthesis features: 1) rapid access to the optically active right‐hand segment starting from the known 5‐hydroxymethyl‐2‐cyclopentenone scaffold; 2) construction of the B and E rings by a key intramolecular tandem radical cyclization; 3) formation of the hemiacetal moiety in the C ring through the α‐oxidation of the six‐membered lactone followed by methanolysis.     

Asymmetric Synthesis of Bryostatin 2

The potent bryostatin antitumor agents are currently in phase II clinical trials for the treatment of a variety of forms of cancer. Aldol reactions and directed reductions are among the essential steps for the formation of fragments A – C in the total synthesis of the title compound. Coupling of these fragments by sulfone-based olefination and alkylation reactions was followed by macrocyclization and introduction of the enoate moieties on rings B and C .     

Synthesis of Asymmetric Propanetriol Analogues

Form natural tartaric acid,(R)-2-benzyloxy-3-(2-tertrahydropyranyloxy) propanol 3 was designed and synthesized, and (R)-2-benzyloxy-3-(4-methoxybenzyloxy)propanol 7 was prepared in a new method. They can be used as chiral synthons of lysophosphatidic acid and other compounds with asymmetric propanetriol backbone.     

二氟甲基取代氮杂环丙烷的不对称合成

以(S)-叔丁基亚磺酰胺和二氟取代酮为原料制得8个二氟甲基取代的叔丁基亚磺酰亚胺(2a~2h);2a~2h与硫叶立德经不对称加成反应合成了12个二氟甲基取代的叔丁基亚磺酰基氮杂环丙烷(3a~3h),其结构经1H NMR,13C NMR,19F NMR,FT-IR和HR-ESI-MS确证。     

色满衍生物的不对称合成

含有色满环(2H-1-苯骈吡喃-3,4-二氢)结构的天然产物有抗氧化,抗病毒,免疫,强壮神经等功能。合成这类中间体结构,很早就为人们所关注。早期根据生源合成理论,将异戊二烯和酚反应,在路易斯酸存在下合成出色满衍生物。此后在这方面作过许多工作。     

维生素E的不对称合成

系统地综述了维生素E的合成方法, 旨在为进行维生素E及其相关萜类化合物合成的研究人员提供参考.     

Catalytic Asymmetric Synthesis of Isoindolinones

As important reactive species, isoindolinones represent a cluster of valuable building blocks for the construction of natural‐product‐like compounds. In particular, chiral isoindolinones are the key structural feature of naturally occurring bioactive molecules. During the past decade, great advances have been made in the asymmetric synthesis of isoindolinone skeleton compounds. Hence, recent progress in catalytic asymmetric synthesis of isoindolinones is reviewed here, with emphasis on chiral organocatalysis and transition metal complexes enabled transformations. Different organocatalysts (chiral phosphoric acids, phase transfer catalysts, chiral thioureas) and chiral transition‐metal complexes (Rh, Pd, Ir, Cu, Mg, and Ni) are included in this transformation.     

5-Hexadecanolide的不对称合成

Optically pure S-5-hexadecanolide （1） has been easily prepared from readily available aldehyde 2 and cyclopentanone （3） using L-proline-catalyzed asymmetric aldol reactions as the key step.