由(1R, 2S)-麻黄碱制备的硼杂恶唑烷催化甲硼烷不对称还原苯乙酮

由(1R, 2S)-麻黄碱制得了五个新的手性硼杂恶唑烷1~5, 它们催化甲硼烷不对称还原苯乙酮, 获得了高产率的具有38.5~72.4%e. e.的R-1-苯基乙醇。讨论了催化剂的结构-活性关系及反应参数(催化剂用量、反应温度)对还原对应对映选择性的影响。     

(R)-α-烷基糠胺的不对称合成

本文通过(+)-樟脑缩呋喃甲亚胺的不对称烷基化反应, 合成了(R)-α)-烷基糠胺。反应的非对映选择性经1H NMR测定为5～67%(d.e)。用1, 3-二碘丙烷和α, α-二溴邻二甲苯作烷基化试剂, 得到预期的双亚胺烷基产物, 而用1,2-二溴乙烷时,却给出偶联产物。     

(-)-莰烷磺内酰胺法合成(S)和(R)切叶蚁警界信息素

本文以樟脑衍生物(-)-莰烷磺内酰胺(2)为原料，经N-烷酰基莰烷-2,10-磺内酰胺(3)与碘代烷的不对称烷基化反应，用二锂代乙基苯基砜取代磺内酰胺助剂以及铝汞还原性脱硫反应等三步合成(S)和(R)-切叶蚁警界信息素(1)，其光学纯度高达95%e.e.以上。     

不对称加氢催化剂[Ru(BINAP)(OAc)2]的合成及其固载化研究

对文献报道的实验反应条件进行优化改进后,合成了不对称加氢催化剂[Ru((S)-BINAP)(OAc)2]和[Ru((R)-BINAP)(OAc)2]。将合成的催化剂应用于惕各酸的不对称催化氢化,(S)-2-甲基丁酸得率为88%,立体选择性可达85%e.e.。为了提高催化剂的利用率,将催化剂[Ru(BINAP)(OAc)2]负载在新型介孔分子筛SBA-15上,用于惕各酸的不对称催化氢化,循环应用3次后,(S)-2-甲基丁酸得率仍可达到59%,立体选择性达57%e.e.。     

(S)-(+)-姜黄烯的立体选择性全合成

利用不对称双羟化反应和Raney镍的原位还原,高对映选择性和高产率地实现了(S)-(+)-α-姜黄烯(1)的立体选择性合成.用MsCl保护化合物7a和7b时,发现了有趣的消除和重排反应,得到对应的二烯化合物8.     

多功能光学活性丁二醇衍生物的合成和结构

通过新的合成策略,以手性合成子3和具有生物活性的有机碱类化合物4为反应底物,利用Michael不对称加成反应,合成得到光学纯的5-(R)-［(1R,2S,5R)-(-)-氧基］-4-(R)-(杂环碱基)-2(5H)-呋喃酮(5). 加成物5通过还原反应得到了多功能光学活性的二醇类化合物6,产率为42%~82%,e.e.≥98%. 化合物6的化学结构得到了确认,其立体化学结构和绝对构型经X射线晶体学测定得到了确定.     

(R)-α-烷基糠胺的不对称合成

本文通过(+)-樟脑缩呋喃甲亚胺的不对称烷基化反应,合成了(R)-α-烷基糠胺。反应的非对映选择性经~1H NMR测定为5～67％(d.e.).用1,3-二碘丙烷和α,α-二溴邻二甲苯作烷基化试剂,得到预期的双亚胺烷基产物,而用1,2-二溴乙烷时,却给出偶联产物。     

脱氢姜黄烯及其类似物的合成

利用苯乙酮及苯乙酮衍生物,经过傅-克乙酰化反应、偶联反应、Wittig烯化反应,合成了脱氢姜黄烯及其类似物.再经选择性催化氢化反应,可分别得到α-姜黄烯、黄根醇甲醚及姜黄氢醌甲醚.     

(S)-(-)-5-对苄氧基苄基-2,4-噁唑烷二酮的合成

L-酪氨酸经O-苄基化和重氮化反应得到关键中间体--手性3-(对苄氧基苯基)-α-羟基丙酸(4); 4经酯化、氨化和环化反应合成了(S)-(-)-5-对苄氧基苄基-2,4-噁唑烷二酮,总收率10%, 95.4%e.e.,其结构经1H NMR和HR-MS表征.     

(-)-莰烷磺内酰胺法立体选择性合成米象虫和玉米象虫聚集合信息素

本文以(-)-莰烷-2, 10-磺内酰胺(2)为原料经六步反应立体选择性地合成了米象虫和玉米象虫聚集信息素(4S, 5R)-Sitophilure, 两个手性中心是由N-丙酰基-莰烷-2, 10-磺内酰胺(3)与丙醛进行的不对称顺式醛醇缩合反应一次性引入的。该全合成的对映异构体纯度可达96%e.e。     

胶束模拟酶的研究2:手性胶束中硫醚氧化为亚砜的不对称诱导

从(+)-和(-)-α-甲基苄胺和天然麻黄素(ephedrine)合成三个手性表面活性剂,由这些表面活性剂组成的手性胶团体系可用作最简单的酶模型和立体专一性催化的研究,在手性胶团体系中,手性亚砜可以用NaIO4或H2O2不对称氧化硫醚而获得,讨论了表面活性剂结构与不对称诱导之间的关系.     

昆虫性信息的结构鉴定与合成 XXVII: (5R, 6S)-(-)-及(5S, 6R)-(+)-淡色库蚊产卵引诱性信息素的立体选择性合成与手性亚砜不对称加成的立体化学

从R-(-)-正十三烯-3-醇2所得的R-(+)-醛5, 与R-(+)亚砜化合物6的不对称醇醛缩合得7a和7b(30:1). 7a经一系列转化得1a, 从(5S, 6R)-14出发, 经两次构型翻转[5S,6R)-15→(5S, 6S)-16和(5S, 6S)-17→(5R, 6S)-14], 得1a的对映体1b. 光学活性α-苄氧基醛5与手性亚砜的不对称醇醛缩合, 受手性亚砜的1,3-不对称诱导控制, 而不是受醛5的1,2-不对称诱导控制.     

N-(甘氨酸薄荷酯)-(+)-樟脑亚胺在烷基化反应中的双手性诱导效应

本文报道了从(+)-樟脑与(+)或(-)-甘氨酸薄荷醇酯所得的亚胺的烷基化反应, 烷基化产物经水解得到(R)-氨基酸。与N-(特丁氧羰基亚甲基)-(+)-樟脑亚胺相比,由于存在匹配的双手性诱导效应, 而使N-[甘氨酸-(+)-薄荷酯]-(+)-樟脑亚胺烷基化的立体选择性有明显的提高(43.8-98%),而不匹配的N-[甘氨酸-(-)-薄荷醇酯]-(+)-樟脑亚胺烷基化的立体选择性明显降低。它们的甲基化都给出(S)-丙氨酸, 且立体选择性不受薄荷酯的构型影响。     

以(+)-樟脑缩苄胺作中间体对映选择合成(R)-α-取代苄胺

本文报道以(+)-樟脑作手性助剂, 苄胺为原料, 二者缩合制得的酮亚胺作中间体3,不对称合成(R)-α-取代苄胺(7)的一条有效新途径。化合物3用丁基锂去质子化提供的锂衍生物4和卤代烷反应, 以较高立体选择性产生烷基化产物6, 化合物6用醋酸羟胺转氨反应后, 获得了光学产率为4.6-90%的(R)-α-取代苄胺(7), 以肟的形式回收(+)-樟脑。     

Total synthesis of natural (+)-(2's,3'r)-zoapatanol

[reaction: see text] (+)-Zoapatanol was synthesized by using four key-steps: a Suzuki cross-coupling to prepare a (Z)-alpha,beta-unsaturated ester followed by an enantioselective dihydroxylation to control the C2' and C3' stereocenters, an intramolecular Horner-Wadsworth-Emmons olefination to construct the oxepane ring, and a chemoselective nucleophilic addition/Birch reduction process of a Weinreb amide to introduce simultaneously the beta,gamma-unsaturated ketone on the side-chain and regenerate alcohols from benzyl ethers.     

(R)-(+)-β-Veratryl-γ-butyrolactone. A new key-intermediate for the asymmetric synthesis of various lignans

Methyl α-veratrylhemisuccinate was resolved into its (R)-(+) and (S)-(−) antipodes by (S)-(−) and (R)-(+)-α-methylbenzylamine respectively. Calcium borohydride reduction of the (R)-(+)-hemiester afforded (R)-(+)-β-veratryl-γ-butyrolactone. The latter was used for the synthesis of various naturlly occurring lignans such as (+)-dimethylisolariciresinol, (−)-kusunokinin and (−)-dimethylmatairesinol.     

An easy preparation of (−) and (+)-β-piperonyl-γ-butyrolactones,key-intermediates for the synthesis of optically active lignans

Methyl α-piperonylhemisuccinate was resolved into both its (R)-(+) and (S)-(?)-antipodes by (?) and (+)-ephedrine, respectively. Calcium borohydride reduction of the (R)-(+) and (S)-(?)-hemiesters afforded the crystalline, optically pure, (R)-(+) and (S)-(?)-β-piperonyl-γ-butyrolactones, respectively, and in high yields. The latter were converted into (?) and (+)-isodeoxypodophyllotoxin, respectively.     

Constructing conformationally constrained macrobicyclic musks

To investigate the structure-odor correlation of musks, (12R)-12-methyl-13-tridecanolide (1), a macrocyclic musk, and 13-tridecanolide, its non-musky demethyl analogue, were conformationally constrained by introduction of methylene bridges between C-3 and C-8 or C-9. These [7.5.1]- and [8.4.1]-macrobicycles were synthesized starting from bicyclo[5.3.1]undec-8-en-9-one (3) and bicyclo[4.3.1]dec-7-en-8-one (8), respectively, by a sequence consisting of catalytic hydrogenation, alpha-alkylation with a TBS-protected (tert-butyldimethylsilyl) hydroxy halide, acid-catalyzed cyclization, oxidative cleavage of the formed enol ether double bond, and subsequent reduction of the carbonyl group via its tosylhydrazone. The compound (1R,6R,9R)-(+)-6-methyl-4-oxa-bicyclo[7.5.1]pentadecan-3-one (22) was found to possess the most pronounced musk odor, and this was rationalized by a superposition analysis with the polycyclic aromatic musk odorant (4S,7R)-Galaxolide (2). In its (1S,6R,9S)-(+)-stereoisomer 23 as well as in (1S,6R, 10R)-(+)-6-methyl-4-oxabicyclo[8.4.1]-pentadecan-3-one (18) the (6R)-methyl group seems to hinder the interaction with the musk receptor, while the demethyl compounds 7 and 12 showed only very faint odors.     

2,2'-二乙炔基-1,1'-联萘为模板构筑的新的环芳化合物的合成及其光学性质

基于2,2'-二取代的联萘衍生物在手性构型上高度稳定的特点,分别以光学活性的(R)-和(S)-2,2'-二乙炔基-1,1'-联萘为模板,设计了2个有趣的拓扑环芳分子四联萘笼状对映异构体(R,R,R,R)-2和(S,S,S,S)-2.其合成路线涉及保护基的控制导入、苯连接桥的链接、保护基的脱去以及偶合成环反应4个步骤.用MS,IR,UV-Vis,1HNMR,13CNMR和元素分析等技术对其进行了表征,并比较了其光学性质.研究结果表明,采用这种模板合成方法能够有效地获得具有单一手性的目标化合物.镜像特征的圆二色(CD)谱和比旋光度[α]D的测定结果清楚地反映了它们的对映异构关系.     

Synthesis of a sterically crowded atropisomeric 1,8-diacridylnaphthalene for dual-mode enantioselective fluorosensing

An efficient synthetic route to a sterically crowded 1,8-diheteroarylnaphthalene-derived enantioselective fluorosensor that operates in two different detection modes utilizing fluorescence lifetime and intensity has been developed. Screening of palladium-catalyzed Negishi, Kumada, Suzuki, Hiyama, and Stille coupling methods showed that the latter affords highly congested 1,8-diarylnaphthalenes in superior yields. Despite severe steric hindrance, axially chiral 1,8-bis(3-(3',5'-dimethylphenyl)-9-acridyl)naphthalene, 1, was obtained in 68% yield from 1,8-dibromonaphthalene, 14, and 3-(3',5'-dimethylphenyl)-9-tributylstannylacridine, 13, via two consecutive Stille cross-coupling steps using tetrakis(triphenylphosphine)palladium(0) as catalyst in the presence of copper(II) oxide. The preparation of 1 involved formation of 4-(3',5'-dimethylphenyl)-2-chlorobenzoic acid, 7, through microwave-assisted Suzuki coupling of 4-bromo-2-chlorobenzoic acid, 10, and 3,5-dimethylphenylboronic acid, 11, followed by regioselective amination with aniline and acridine ring construction in phosphorus oxybromide. Lithiation, subsequent treatment with trimethylstannyl chloride, and Stille cross-coupling then completed the five-reaction sequence providing 1 in 57% overall yield. The enantiomers of 1 were separated by semipreparative HPLC on a (R,R)-Whelk-O 1 column and successfully employed in enantioselective fluorosensing of N-t-Boc-protected serine, 20, glutamine, 22, proline, 23, and 2-hydoxy-2-methylsuccinic acid, 21. Fluorescence titration experiments with 23 revealed that both static and dynamic quenching occur with distinctive enantioselectivity. Addition of (R)-23 to a solution of (+)-1 in acetonitrile resulted in stronger fluorescence quenching than titration with the (S)-enantiomer of 23. The fluorescence lifetime, tau, of 1 was determined as 18.8 ns and steadily decreased to 7.5 and 6.8 ns in the presence of 0.1 M of (S)-23 and (R)-23, respectively.