关键词： asymmetric catalysis   cinchona alkaloids   natural products   phase-transfer catalysis   vinylic substitution  

摘要： A goodstarting point: Optically pure glactams have been prepared by organocatalytic enantioselective vinylic substitution. The parent lactam structure allows logical and systematic introduction of functionality around the periphery to access new derivatives of this important class of molecules. Bn = benzyl, PG = protecting group. (Chemical Equation Presented) © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

关键词： D-RIBO-PHYTOSPHINGOSINE   STEREOSELECTIVE TOTAL-SYNTHESIS   D-ERYTHRO-SPHINGOSINE   ENANTIOSELECTIVE TOTAL-SYNTHESIS   INTRAMOLECULAR N-ALKYLATION   PIPERIDINE RING FORMATION   CHIRAL BUILDING-BLOCK   CYTOTOXIC ANHYDROPHYTOSPHINGOSINE   EFFICIENT SYNTHESIS   FORMAL SYNTHESIS  

摘要： The highly diastereoselective anti-aminohydroxylation of (E)-gamma-tri-iso-propylsilyloxy-alpha,beta-unsaturated esters, via conjugate addition of lithium (S)-N-benzyl-N-(alpha-methylbenzyl) amide and subsequent in situ enolate oxidation with (+)-(camphorsulfonyl) oxaziridine, has been used as the key step in the asymmetric synthesis of N,O,O,O-tetra-acetyl D-lyxo-phytosphingosine (20% yield over 7 steps), the anhydrophytosphingosine jaspine B (10% yield over 9 steps), 2-epi-jaspine B (14% yield over 9 steps), and the Prosopis alkaloid deoxoprosophylline (26% yield over 7 steps).

关键词： ALPHA   GAMMA-SUBSTITUTED GAMMA-BUTYROLACTONES   TERT-BUTANESULFINYL IMINES   CATALYTIC ENANTIOSELECTIVE PROTONATION   ALPHA-HETEROSUBSTITUTED KETONES   MEDIATED ORGANIC-SYNTHESIS   BETA-AMINO ALCOHOLS   CARBONYL-COMPOUNDS   RADICAL REACTIONS   CHIRAL AUXILIARY   SMI2-MEDIATED CYCLIZATION  

摘要： Samarium diiodide may be a useful reagent in a step of an asymmetric synthesis process. It can release a blocking group in mild conditions, as described in several examples. SmI2 has been used as electron donor in many C - C bond formations in presence of a chiral auxiliary. It can also generate samarium enolates which were subjected to asymmetric protonation. The examples selected in this review of SmI2 methodology concern only the cases where the chiral auxiliary is not retained in the final product.

关键词： antifungal agents   asymmetric synthesis   cytotoxicity   natural products   total synthesis  

摘要： Leucascandrolide A (1) is a novel macrolide possessing an unusual dioxotricyclic core, which displays potent cytotoxic activity against KB (throat epithelial cancer, IC_(50) = 0.05 μgmL~(-1)) and P388 (murine leukemia, IC_(50) = 0.25 μgmL~(-1)) tumor cell lines, in addition to antifungal activity against Candida albicans. The latter feature is particularly important given the growing concern among AIDS patients with regard to infections from this animal-pathogenic yeast. Interestingly, the cytotoxic activity of 1 can primarily be attributed to the macrolide moiety, whereas the antifungal activity derives from the oxazole side chain. Hence, the ability to construct this agent in a more expeditious manner would provide the opportunity to conduct more detailed structure-activity studies and potentially capitalize on this divergent behavior. Although this agent was originally isolated from the calcareous sponge Leucascandra caveolata in the Coral Sea by Pietra and co-workers, subsequent attempts to isolate the material have failed. This has led to speculation with respect to the actual source of this agent, which has tentatively been attributed to opportunistic bacteria colonizing a decayed portion of the sponge rather than a more classical symbiotic relationship. Hence, the unique molecular architecture and potent biological activity, coupled with the lack of bioavailability from natural sources, have inspired several outstanding syntheses of this important *** these approaches have significant merit, both in terms of their strategic and methodological developments, they each construct the key 1,5-bis(tetrahydropyran) moiety in a stepwise manner.

关键词： Bitungolides A-F   不对称合成   Evans烷基化反应和Aldol反应   不对称的双羟化反应   Myers烷基化反应   TBPA+·SbCl6-   脱保护   TBS   THP  

摘要： 本论文主要对二氢吡喃酮类天然产物Bitungolides A-F进行了不对称合成研究,同时还对TBPA+·SbCl6-氧化脱除叔丁基二甲基硅醚（TBS）和四氢吡喃（THP）醚进行了研究。总共包括下面四个部分: 第一章手性辅基在有机合成中的应用（综述） 手性辅基的介绍及在有机合成中的应用 第二章Bitungolides A-E的不对称合成研究 以Evans模版的烷基化反应和Aldol反应、不对称的烯丙基化反应、不对称的双羟化反应和Myers烷基化反应为关键步骤,方便的建立了bitungolides A-E中的六个手性中心,经过17步反应以总产率为4.7%合成了bitungolides A-E的核心骨架,为今后进行bitungolidesA-E的全合成奠定了基础。 第三章:Bitungolide F的不对称合成研究 以廉价易得的天然苹果酸为起始原料,以羟基诱导的还原反应、Myers甲基化反应、Evans Aldol反应、Julia反应为关键步骤得到了目标天然产物BitungolideF的前体,对Bitungolide F的合成进行了探索。 第四章:TBPA+·SbCl6-氧化脱除叔丁基二甲基硅醚（TBS）和四氢吡喃（THP）醚 简要介绍了氧化脱除叔丁基二甲基硅（TBS）醚的研究进展。 以催化量TBPA+·SbCl6-氧化脱除叔丁基二甲基硅（TBS）醚和四氢吡哺（THP）醚,对反应条件进行了优化,并对其机理进行了探讨。

关键词： 动力学拆分   20(S)-喜树碱类药物   拓扑异构酶抑制剂   手性辅助剂   不对称合成  

摘要： 目的 合成20(S)-喜树碱类抗肿瘤药物关键中间体5'(S)-1,1-亚乙二氧基-5-氧代-(5'-乙基5'-羟基-2'H,5'H,6'H-6-氧代吡喃)-[3',4'-f]-△'6(8)-四氢中氮茚.方法 以1,1-亚乙二氧基-5-氧代-(5'-乙基-2'H,5'H,6'H-6-氧代吡喃)-[3',4'-f]-△'6(8).四氢中氮茚为原料,经碘催化氧化、动力学拆分、碱水解3步得到光学纯目标化合物.结果与结论 该合成路线操作简单,总收率15.7%,ee值96%.

关键词： sulfinimine (N-sulfinyl imine)   asymmetric synthesis   1,3-dithiane   cathinone   alpha-amino ketones   N-protection   epimerization  

摘要： The asymmetric synthesis of N-tosyl cathinone, a high reactive alpha-amino ketone, via the addition of 2-lithio-2-phenyl-1,3-dithiane to a sulfinimine (N-sulfinyl imine), is described. It was found that the resistance of N-tosyl alpha-amino ketones to epimerization is related to the ability of this protecting group to stabilize anions at nitrogen.

关键词： 拉米夫定   衍生物   HIV   HBV   合成  

摘要： 拉米夫定是人类免疫缺陷病毒逆转录酶（HIV-RT）抑制剂,最初用于治疗HIV感染,以后发现对于乙型肝炎病毒（HBV）复制具有抑制作用。拉米夫定因其具有良好的耐受性、安全性和服用方便等特点,已广泛应用于临床。抗人类免疫缺陷病毒、乙型肝炎病毒治疗的新药研究和现有有效药物的工艺改进等工作已经列为目前的抗病毒药物研究的重中之重,也是目前国家经济贸易委员会推荐方向。 本文首先简述了HIV、HBV所引起的疾病、流行病学研究及防治,核苷类抗病毒药物及其研究状况等。在现有的文献基础上,选择了一条合理的拉米夫定合成工艺路线,对各步反应条件进行了优化,使其获得较高的质量和产率。 本路线有四步反应,主要中间体经由水合乙醛酸经酯化、缩合、取代、糖基化、还原等过程。各中间体及目标产物,利用熔点测定,质谱,核磁共振（1H-NMR）等确证了其化学结构。 本工艺,在第一步通过确定了合适的投料比及催化剂H2SO4的量,第二步通过改进减少回流这一过程,使仪器设备更加简化,可操作性更强,是本工艺比较突出的地方;第三步通过改变氯代反应溶剂系统和硅烷化催化剂,使反应目的性更强,能耗更低;第四步以硼氢化钠为还原剂,处理方便,对溶剂要求不高。 研究表明,本工艺制备拉米夫定,原料易得、对设备的要求较低、可操作性强、收率较高,有工业化生产的前景。

关键词： Enantiopure fluorous diamines   asymmetric catalysis   allylic alkylation   hydrogen-transfer reaction  

摘要： The synthesis of a new enantiopure fluorous 1,2-diaryl-1,2-diaminoethane bearing two fluorous ponytails is described. The palladium-catalyzed reaction of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate in the presence of this ligand and its analogue bearing four fluorous ponytails gave the alkylated product with ee up to 44%. Their application as ligands in hydrogen transfer reactions associated with rhodium, iridium, or ruthenium in a two-phase system gave ee up to 39%, the catalyst being recycled without loss of enantioselectivity in the case of the ruthenium complex.

关键词： α-氨基膦酸酯   不对称合成   奎宁   奎宁衍生物   构型  

摘要： α-氨基膦酸酯作为天然氨基酸的类似物,具有抗肿瘤、抗植物病毒、植物生长调节、除草、杀菌、抑制酶活性、抗氧化及防辐射、破坏生物细胞膜等广泛的生物活性而受到很多科学家的关注。通常合成的α-氨基膦酸酯都是以外消旋体形式存在的,而其生物活性与它的绝对构型有密切关系,所以研究这类化合物的不对称合成具有非常重要的意义。 为了研究简单有效合成手性α-氨基膦酸酯的合成方法,本课题首先选择以本中心自主开发的具有抗烟草花叶病毒农药O,O′-二乙基-a-(4-甲基苯并噻唑-2-基)氨基-(2-氟苯基)甲基膦酸酯(“病毒星”)为目标化合物,以奎宁为手性催化剂,通过改变温度、溶剂和催化剂用量等反应条件,筛选出了此反应的最佳反应条件(反应温度:20℃;反应溶剂:二甲苯;催化剂用量:20 mol%;加入一定量的4(?)分子筛)。在最佳反应条件下得到的目标产物“病毒星”ee值最高达41%。同时,我们对奎宁催化剂进行了一系列衍生,得到相应的酯化、醚化、甲氧基还原化等系列衍生物催化剂,并分别对它们进行了结构表征及催化活性测试,结果发现当奎宁的9-羟基被酯化或醚化后的衍生物在相同条件下不能催化此反应,而当奎宁的6′-甲氧基被还原后的衍生物在相同条件下得到了主要异构体构型完全相反的目标产物,ee值为-32%。当改变反应底物亚磷酸酯时,得到的相应产物ee值均不高,而当用不含杂原子的简单亚胺或异噁唑亚胺与亚磷酸乙酯反应时,反应不进行,这可能与底物亚胺结构中所含杂原子有关。最后,我们进行了相关的理论研究工作,通过理论计算我们发现可能是由于含苯并噻唑的亚胺在反应中经历的生成不同构型产物的过渡态的能量差别较小,因此反应的对映选择性低。