从(一)-α-蒎烯合成(1R,3R)-(+)-反式菊酸甲酯

本文报道了以(-)-α-蒎烯为主要成分的松节油作原料,通过十四步反应合成了(1R,3R)-(+)-反式菊酸甲酯,每步反应的得率都在60％以上,总得率10.8％.反应操作方便,条件温和,对合成路线中的有些反应作了一些比较和讨论.化合物3—9都是新化合物.     

(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。     

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。     

(2S)-(+)-2-溴-1-(6'-甲氧基-2'-萘基)丙-1-酮的不对称合成

以(2R,3R)-酒石酸二甲酯为手性辅助剂,6-甲氧基-2-丙酰基萘经缩酮化、溴化铜不对称溴化、水解等反应合成了(2S)-2-溴-1-(6'-甲氧基-2'-萘基)丙-1-酮。总收率94%。     

2-氨基-3-羟基环戊烯-1-腈衍生物的合成和晶体结构

用低价钛试剂(TiCl~4-Zn)与α,α-(4-氯苯基)(二氰甲基)甲基苯基酮反应合成了非对映消旋体(3R,5S;3S,5R)和(3R,5R;3S,5S)2-氨基-3-羟基-3-苯基-5-对氯苯基环戊烯-1-腈。并用X射线衍射分析确定了这两个非对映异构体的构型。     

β-(3,4-二羟基苯基)-α-羟基一N-[(R)-3-苯基-1-乙氧酰基丙基]丙酰胺的合成

以3,4-二羟基苯甲醛为原料,经开环、Knoevenagel缩合、水解和Clemmemen还原反应合成了丹参素(5);5与(R)-2-胺基-4-苯基丁酸乙酯在DCC/DMAP作用下,脱去一分子水合成了β-(3,4-二羟基苯基)-α-羟基-N-[(R)-3-苯基-1-乙氧酰基丙基]丙酰胺(8).8的结构经1H NMR,IR和MS表征.     

(-)-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。     

6-(4-取代苯乙烯基)-8-(4-取代苯基)-10,10-二甲基-10H-吡啶并[1,2-a]吲哚盐的合成

通过2,3,3-三甲基-3H-吲哚高氯酸盐与取代双亚苄基丙酮在异戊醇中的反应,合成五种新的6-(4-取代苯乙烯基)-8-(4-取代苯基)-10,10-二甲基-10H-吡啶并[1,2-a]吲哚盐[R=H(3a),Cl(3b),Br(3c),MeO(3d),Me_2N(3e)]。     

3-疏基香豆素及其衍生物的研究

研究了3-疏基香豆素(8)、3,3'-二硫代双香豆素的合成及8与一系列Michael受体的反应.按受体结构不同,除都能发生分子间的加成反应外,有些还可进一步发生第二次分子内的加成反应,关环后得到一系列四氢噻吩并[2,3-C][1]苯并吡喃-4(H)-酮的衍生物.对这些化合物的立体化学及结构进行了鉴定.8分别和烯丙基溴、肉桂基溴缩合,前者在N,N-二甲苯胺内发生正常的Claisen重排,得到1,2-二氢-2-甲基噻吩并[2,3-C][1]苯并吡喃-4-(H)-酮及1,2,3,5-四氢硫代吡喃并[2,3-C][1]苯并吡喃-5-酮,但后者的反应产物是3-(ρ-N,N-二甲氨基)苄硫基香豆素.     

采用通透性处理的安大略假丝酵母全细胞高效合成(R)-2-氯-1-(3-氯苯基)乙醇(英文)

考察了利用安大略假丝酵母(Candida ontarioensis)静息细胞不对称催化2-氯-1-(3-氯苯基)乙酮合成(R)-2-氯-1-(3-氯苯基)乙醇的转化反应条件.结果表明,当底物浓度为10g/L时,在最适转化条件下反应72h,产物的ee值和产率分别达到99.9%和99.0%.采用4g/L十六烷基三甲基溴化铵对Candida ontarioensis细胞于4℃通透性处理20min后,全细胞的酶活提高2倍以上.当底物浓度提高为30g/L,转化24h后,产物的ee和产率分别达到99.9%和97.5%.该研究为高效制备(R)-2-氯-1-(3-氯苯基)乙醇提供了可行途径,并为生物催化合成芳基手性醇类手性中间体提供了理论指导。     

(R)-3-叔丁基二甲基硅氧丁基苯硫醚的合成方法改进

以4-(二甲氨基)吡啶为催化剂,通过(R)-3-叔丁基二甲基硅氧丁醇与甲磺酰氯之间的改进烷基磺酰化反应得到(R)-3-叔丁基二甲基硅氧丁基甲磺酸酯(2b,收率98%),2b再与苯硫酚钠反应生成(R)-3-叔丁基二甲基硅氧丁基苯硫醚(3,总收率89%)。2和3的结构经1H NMR,IR和MS表征。     

Chiroptical properties of (R)-3-chloro-1-butene and (R)-2-chlorobutane

Coupled cluster and density functional models of specific rotation and vacuum UV (VUV) absorption and circular dichroism spectra are reported for the conformationally flexible molecules (R)-3-chloro-1-butene and (R)-2-chlorobutane. Coupled cluster length- and modified-velocity-gauge representations of the Rosenfeld optical activity tensor yield significantly different specific rotations for (R)-3-chloro-1-butene, with the latter providing much closer comparison (within 3%) to the available gas-phase experimental data at 355 and 633 nm. Density functional theory overestimates the experimental rotations for (R)-3-chloro-1-butene by approximately 80%. For (R)-2-chlorobutane, on the other hand, all three models give reasonable comparison to experiment. The theoretical specific rotations of the individual conformers of (R)-3-chloro-1-butene are much larger than those of (R)-2-chlorobutane, in disagreement with previous studies of the temperature dependence of the experimental rotations in solution. Simulations of VUV absorption and circular dichroism spectra reveal large differences between the coupled cluster and density functional excitation energies and the rotational strengths. However, while these differences lead to very different specific rotations for (R)-3-chloro-1-butene, they have much less impact on the computed specific rotations for (R)-2-chlorobutane. In addition, the coupled cluster VUV absorption spectrum of (R)-2-chlorobutane compares well to experiment.     

Asymmetric synthesis of (1R,2S,3R)-3-methylcispentacin and (1S,2S,3R)-3-methyltranspentacin by kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate

Conjugate addition of lithium dibenzylamide to tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate occurs with high levels of stereocontrol, with preferential addition of lithium dibenzylamide to the face of the cyclic alpha,beta-unsaturated acceptor anti- to the 3-methyl substituent. High levels of enantiorecognition are observed between tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate and an excess of lithium (+/-)-N-benzyl-N-alpha-methylbenzylamide (10 eq.) (E > 140) in their mutual kinetic resolution, while the kinetic resolution of tert-butyl (+/-)-3-methylcyclopentene-1-carboxylate with lithium (S)-N-benzyl-N-alpha-methylbenzylamide proceeds to give, at 51% conversion, tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate consistent with E > 130, and in 39% yield and 99 +/- 0.5% de after purification. Subsequent deprotection by hydrogenolysis and ester hydrolysis gives (1R,2S,3R)-3-methylcispentacin in > 98% de and 98 +/- 1% ee. Selective epimerisation of tert-butyl (1R,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate by treatment with KO'Bu in 'BuOH gives tert-butyl (1S,2S,3R,alphaS)-3-methyl-2-N-benzyl-N-alpha-methylbenzylaminocyclopentane-1-carboxylate in quantitative yield and in > 98% de, with subsequent deprotection by hydrogenolysis and ester hydrolysis giving (1S,2S,3R)-3-methyltranspentacin hydrochloride in > 98% de and 97 +/- 1% ee.     

Synthesis of (R)-2-methyl-4-deoxy and (R)-2-methyl-4,5-dideoxy analogues of 6-phosphogluconate as potential inhibitors of 6-phosphogluconate dehydrogenase

The synthesis of (2R)-2-methyl-4,5-dideoxy and (2R)-2-methyl-4-deoxy analogues of 6-phosphogluconate is described. The synthetic strategy relies on the Evans aldol reaction for the installation of the chiral centres in the 2- and 3-positions. The selective phosphorylation at the primary alcohol function of (2R,3S)-3,6-dihydroxy-2-methylhexanoic acid benzyl ester (5) and (2R,3S,5S)-3,5,6-trihydroxy-2-methylhexanoic acid benzyl ester (20) was achieved with dibenzyl phosphochloridate and dibenzyl phosphoiodinate respectively, working at low temperature. (2R,3S)-3-Hydroxy-2-methyl-6-phosphonoxyhexanoic acid (9) was obtained in 25% overall yield from 4-benzyloxybutanol and (2R,3S,5S)-3,5-dihydroxy-2-methyl-6-phosphonoxyhexanoic acid (28) in 10% overall yield from L-malic acid.     

Stereoselective synthesis of (S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile

(S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile (1) is a key intermediate in the preparation of PF-00951966, (1) a fluoroquinolone antibiotic for use against key pathogens causing community-acquired respiratory tract infections including multidrug resistant (MDR) organisms. The current work describes the development of a highly efficient and stereoselective synthesis of 1 in 10 steps with an overall yield of 24% from readily available benzyloxyacetyl chloride. Two key transformations in the synthetic sequence involve (a) catalytic asymmetric hydrogenation with chiral DM-SEGPHOS-Ru(II) complex to afford β-hydroxy amide 11b in good yield (73%) and high stereoselectivity (de 98%, ee >99%) after recrystallization and (b) S(N)2 substitution reaction with methylamine to provide diamine 14 with inversion of configuration at the 1'-position in high yield (80%), after efficient purification using a simple acid/base extraction protocol.     

Total syntheses of beta-carboline alkaloids, (R)-(-)-pyridindolol K1, (R)-(-)-pyridindolol K2, and (R)-(-)-pyridindolol.

The total syntheses of beta-carboline alkaloids, (R)-(-)-pyridindolols (1, 5, and 6) are described. The two key steps involved are (1) a thermal electrocyclic reaction of the 3-alkenylindole-2-aldoxime 10 and (2) a thermal cyclization of 3-alkynylindole-2-aldoxime 11 to construct the beta-carboline N-oxides 8, which upon heating with acetic anhydride and sequential treatment with trifluoromethanesulfonic anhydride gave the triflates 18. The Stille coupling reaction of 18 with vinylstannane, followed by cleavage of MOM ether, afforded the 1-ethenyl-3-hydroxymethyl-beta-carboline (7a). Subsequent acetylation of 7a yielded the acetate 7b, which was subjected to the Sharpless asymmetric 1,2-dihydroxylation by AD-mix-beta to produce (R)-(-)-pyridindolol K2 (6). Selective acetylation of 6 was effected by Ac(2)O and collidine to form (R)-(-)-pyridindolol K1 (5). By contrast, hydrolysis of 6 provided (R)-(-)-pyridindolol (1).     

(+)-(1S,2S,5R)-8-联苯薄荷醇的合成

以(R)-( )-pu legone为起始原料,经1,4-加成,还原两步反应合成了手性辅助试剂( )-(1S,2S,5R)-8-联苯薄荷醇及其差向异构体(-)-(1R,2S,5R)-8-联苯薄荷醇,总产率95%。其结构经1H NMR,13C NMR,IR,MS和X-射线衍射仪表征。     

Asymmetric synthesis of (4R,5R)-cytoxazone and (4R,5S)-epi-cytoxazone

(4R,5R)-Cytoxazone has been prepared in four steps and in 61% overall yield and >98% ee. Conjugate addition of lithium (R)-N-benzyl-N-[small alpha]-methylbenzylamide to tert-butyl (E)-3-(p-methoxyphenyl)prop-2-enoate and subsequent in situ diastereoselective enolate oxidation with (+)-(camphorsulfonyl)oxaziridine gave tert-butyl (2R,3R,[small alpha]R)-2-hydroxy-3-(p-methoxyphenyl)-3-(N-benzyl-N-[small alpha]-methylbenzylamino)propanoate in >98% de. Subsequent N-benzyl deprotection to the primary [small beta]-amino ester via hydrogenolysis, oxazolidinone formation with C(2)-retention by treatment with diphosgene and chemoselective ester reduction furnishes (4R,5R)-cytoxazone. The synthesis of the C(5)-epimer, (4R,5S)-epi-cytoxazone in 44% overall yield, has also been completed via a protocol involving N-Boc protection of the primary [small beta]-amino ester, utilization of the N-Boc group to facilitate simultaneous C(2)-inversion and oxazolidinone formation, and subsequent reduction.     

Asymmetric Synthesis of (3R, 5R)-3-((tert-Butyldimethylsily)oxy)-5-((Z)-2-Bromovinyl)-Tetrahydro-Furan-2-one, an Intermediate for the Synthesis of Fostriecin

Fostriecin(CI-920) 11 a potential anticancer agent presently in phase I clinical trials at NCI is a novel phosphate ester produced by Streptomyces pulveraceus. Scheme 1 1 2 3 5 4 Synthesis of C10 epimer of compound 1 had been reported by Just G2. during the determination of its structure. On the basis of Just’s synthesis, a revised retro-asymmetric synthetic route of Fostriecin (scheme 1) was designed here of which compound 3 was synthesized from 5 with C3 in R configuration correspondi…     

Biopreparation of (-)-(1S,3R,4S,6S)-6-hydroxymenthol and (-)-(1S,3R,4S)-1-hydroxymenthol from 1-menthol by Rhizoctonia solani AG-1-IA and IB

Microbial transformation of 1-menthol (1) by six isolates of soil-borne plant pathogenic fungi Rhizoctonia solani AG-1-IA (Rs24, Joichi-2 and RRG97-1) and AG-1-IB (TR22, R147 and 110.4) as a biocatalyst was investigated. Twenty one days precultivation of Rhizoctonia solani AG-1-IA Rs24 and AG-1-IB 110.4 showed excellent yield (98.5-98.6%) of (-)-(1S,3R,4S,6S)-6-hydroxymenthol (2) and (-)-(1S,3R,4S)-1-hydroxymenthol (3) from 1.