24ζ-甲基-20 S-胆甾醇的合成

已发现的天然甾醇均为20R 构型。近年来在地质体中发现了具有20S 构型的甾烷类生物标志化合物,并称之为地质构型。合成20S 构型的甾烷的方法之一是由20S 构型的甾醇为原料。20S-胆甾醇及20S-胆甾烷的合成已有报道,但24ξ-甲基-20S-     

甾体不对称合成的研究——新光学活性合成原——(2R,3S)-( )-2-乙基-2-(3′-羰基-4′-烯)-戊基-3-乙酰氧基-环戊酮的合成

本文报道一个新的可以广泛应用于甾体全合成的光学活性合成原6的合成.从2-乙基-1,3-环戊二酮 8与 γ-羰基亚砜 12b反应所得之对称三酮 9b经啤酒酵母菌不对称还原得到(2R,3S)-(—)-羟基化合物14,从(2R,3S)-(—)-14所得的(2R,3S)-( )-16的甲磺酸酯或对一甲苯磺酸酯用三乙胺消除即得目的物(2R,3S)-( )-6.微生物不对称还原产生的14的绝对构型是把它转变成已知化合物(2R,3S)-( )-17而得到证明的。     

△~6-6-甲基甾体的合成

本文报告△~6-6-甲基化合物S,△~6-6-甲基可的唑、△~6-6-甲基可的伀及△~6-6-甲基-17α-乙酰氧基黄体酮的合成。     

新型手性二茂铁腙类环钯化合物的合成及其晶体结构

手性二茂铁腙类环钯化合物[(+)-(S)-2-(甲氧基甲基吡咯烷-1-基)-1-乙酰基二茂铁亚胺]在甲醇中与Pd(OAc)2和AcONa·3H2O经不对称环钯化反应合成了两个新型的双-醋酸桥环钯衍生物[syn-(+)-(Rp,S,S,Rp)-3和syn-(+)-(Sp,S,S,Sp)-3];syn-(+)-(Rp,S,S,Rp)-3或syn-(+)-(Sp,S,S,Sp)-3在甲醇中与NaNO2反应合成了两个新型的双亚硝酸桥平面手性环钯化合物[syn-(+)-(Rp,S,S,Rp)-4和syn-(+)-(Sp,S,S,Sp)-4],其结构经1H NMR,元素分析和X-单晶衍射表征。     

16R-溴代孕甾-3S,20S-二醇二乙酸酯与碱的条件可控性反应

为了合理利用甾体皂甙元资源, 系统地考察了16R-溴代孕甾-3S,20S-二醇二乙酸酯在不同反应条件下与碱的反应. 给出了选择性地分别转化16R-溴代孕甾-3S,20S-二醇二乙酸酯成为孕甾-16-烯-3S,20S-二醇二乙酸酯、16R-溴代孕 甾-3S,20S-二醇、孕甾-3S,16S,20S-三醇、孕甾-14,16-二烯-3S-醇乙酸酯和雄甾-16-烯-3S-醇等化合物的可控性反应结果. 这些条件可控性反应结果不仅为甾体药物和生物活性天然甾体化合物合成提供了新的合成中间体, 也为它们新合成策略和途径的设计提供了机遇.     

基于7,7,8,8-四氰基对醌二甲烷-氯化锰反应的二价锰配合物的合成,晶体结构和磁性(英文)

以氯化锰、双二苯基膦酸甲烷(dppm)及7,7,8,8-四氰基对醌二甲烷(TCNQ)为原料,合成了标题化合物[Mn(dppmdo)_3][(TCNQ)(DCBE)]1;利用X射线衍射、红外光谱、紫外-可见-近红外光谱和循环伏安等技术对合成产物进行了表征.结果表明,化合物1在近红外区发生配体TCNQ之间的电子转移(TCNQ/TCNQ~-).化合物1中的TCNQ比游离态的TCNQ分子更容易被还原.室温下,化合物1的有效磁矩(12.7μB)远高于预期的由一个高自旋Mn~(2+)离子(S=5/2)、一个TCNQ(S=1/2)阴离子及一个DCBE(S=1/2)阴离子组成基团的有效磁矩(4.58μB),表明它们之间存在着很强的磁相互作用.     

S-[(1,2,4-三唑-1-基)芳基(或烷基)甲羰]甲基二硫代磷酸酯衍生物的研究

探讨了S-[(1,2,4-三唑-1-基)芳基(或烷基)甲羰]甲基二硫代磷酸酯衍生物的合成方法,合成了12种含三唑有机磷新化合物,通过红外光谱分析,确定该类化合物P=S振动的吸收频率范围为640～680cm^-1,核磁共振氢谱证明,与磷原子相联的基团旋转部分受阻,生物初筛结果表明,部分化合物具有杀菌、除草及植物生长调节活性。     

胆碱酯酶抑制剂(S)-卡巴拉汀及其类似物的不对称合成与活性研究

以对羟基苯甲醛或间羟基苯甲醛为原料,用(R)或(S)-叔丁基亚磺酰胺为手性引发剂,设计合成了(S)-卡巴拉汀及其12个未见文献报道的类似物,其结构通过IR,1HNMR,13CNMR和HRMS确证.以Ellman法进行化合物的活性测试,结果表明合成的化合物都有较好的对乙酰胆碱酯酶以及丁酰胆碱酯酶抑制活性,部分化合物的活性甚至比卡巴拉汀(rivastigmine)更好.     

血癌调节剂—（4S,5R）—5—羟基—4—癸内酯的合成

(4S,5R)-5-羟基-4-癸内酯1对血癌具有调节作用。本文首先利用Sharpless动力学拆分反应制得光学活性的环氧化合物,然后再通过其它反应合成具有生理活性的化合物1。     

AZD0914关键中间体(2R,6R)-2,6-二甲基吗啉的合成工艺研究

(2R,6R)-2,6-二甲基吗啉（1）为合成新型细菌II型拓扑异构酶抑制剂AZD0194(Zoliflodacin)的关键中间体。本文以(S)-2-羟基丙酸乙酯（12）为原料,经三氟甲磺酰化、S_N2反应、硼氢化钠还原、对甲苯磺酰化、环合、成盐、催化氢解、游离和蒸馏提纯等步骤,成功合成了化合物1。经过对合成路线中反应条件及提纯方法的优化,以6步反应且总收率为32%获得化合物1。     

An Expedient Approach to the Benzopyran Core: Application to Synthesis of the Natural Products(±)-Xyloketals and(±)-Alboatrin

A mild and efficient protocol for the synthesis of the benzopyran ring has been described and a series of chromans compounds is reported, the yield is from 72% to 95%. The diadduct tended to angular product and showed good regioselectivity. This strategy was applied for the benzopyran derived natural products (±)‐xyloketals and (±)‐alboatrin. The crystal of compound 9 exhibited centro‐symmetric space group, containing two isomers in one unit. The relative configurations were 1R,10R,15S and 34S,22R,30S, respectively.     

Total Synthesis,Stereochemical Assignment,and Field‐Testing of the Sex Pheromone of the Strepsipteran Xenos peckii

The sex pheromone of the endoparasitoid insect Xenos peckii (Strepsiptera: Xenidae) was recently identified as (7E,11E)‐3,5,9,11‐tetramethyl‐7,11‐tridecadienal. Herein we report the asymmetric synthesis of three candidate stereostructures for this pheromone using a synthetic strategy that relies on an sp³–sp² Suzuki–Miyaura coupling to construct the correctly configured C7‐alkene function. Comparison of ¹H NMR spectra derived from the candidate stereostructures to that of the natural sex pheromone indicated a relative configuration of (3R*,5S*,9R*). Chiral gas chromatographic (GC) analyses of these compounds supported an assignment of (3R,5S,9R) for the natural product. Furthermore, in a 16‐replicate field experiment, traps baited with the synthetic (3R,5S,9R)‐enantiomer alone or in combination with the (3S,5R,9S)‐enantiomer captured 23 and 18 X. peckii males, respectively (mean±SE: 1.4±0.33 and 1.1±0.39), whereas traps baited with the synthetic (3S,5R,9S)‐enantiomer or a solvent control yielded no captures of males. These strong field trapping data, in combination with spectroscopic and chiral GC data, unambiguously demonstrate that (3R,5S,9R,7E,11E)‐3,5,9,11‐tetramethyl‐7,11‐tridecadienal is the X. peckii sex pheromone.     

Determination of Absolute Configuration of Decipinone,a Diterpenoid Ester with a Myrsinane‐Type Carbon Skeleton,by NMR Spectroscopy

The absolute configuration of decipinone ( 2 ), a myrsinane‐type diterpene ester previously isolated from Euphorbia decipiens, has been determined by NMR study of its axially chiral derivatives (aR)‐ and (aS)‐N‐hydroxy‐2′‐methoxy‐1,1′‐binaphthalene‐2‐carboximidoyl chloride ((aR)‐MBCC ( 3a ) and (aS)‐MBCC ( 3b )). The absolute configurations at C(7) and C(13) of 2 determined were (R) and (S), respectively. Therefore, considering the relative configuration of 2 , the absolute configuration determined was (2S,3S,4R,5R,6R,7R,11S,12R,13S,15R).     

Chiral Heterospirocyclic 2H‐Azirin‐3‐amines as Synthons for 3‐Amino‐2,3,4,5‐tetrahydrofuran‐3‐carboxylic Acid and Their Use in Peptide Synthesis

The heterospirocyclic N‐methyl‐N‐phenyl‐5‐oxa‐1‐azaspiro[2.4]hept‐1‐e n‐2‐amine (6 ) and N‐(5‐oxa‐1‐azaspiro[2.4]hept‐1‐en‐2‐yl)‐(S)‐proline methyl ester ( 7 ) were synthesized from the corresponding heterocyclic thiocarboxamides 12 and 10 , respectively, by consecutive treatment with COCl₂, 1,4‐diazabicyclo[2.2.2]octane, and NaN₃ (Schemes 1 and 2). The reaction of these 2H‐azirin‐3‐amines with thiobenzoic and benzoic acid gave the racemic benzamides 13 and 14 , and the diastereoisomeric mixtures of the N‐benzoyl dipeptides 15 and 16 , respectively (Scheme 3). The latter were separated chromatographically. The configurations and solid‐state conformations of all six benzamides were determined by X‐ray crystallography. With the aim of examining the use of the new synthons in peptide synthesis, the reactions of 7 with Z‐Leu‐Aib‐OH to yield a tetrapeptide 17 (Scheme 4), and of 6 with Z‐Ala‐OH to give a dipeptide 18 (Scheme 5) were performed. The resulting diastereoisomers were separated by means of MPLC or HPLC. NMR Studies of the solvent dependence of the chemical shifts of the NH resonances indicate the presence of an intramolecular H‐bond in 17 . The dipeptides (S,R)‐ 18 and (S,S)‐ 18 were deprotected at the N‐terminus and were converted to the crystalline derivatives (S,R)‐ 19 and (S,S)‐ 19 , respectively, by reaction with 4‐bromobenzoyl chloride (Scheme 5). Selective hydrolysis of (S,R)‐ 18 and (S,S)‐ 18 gave the dipeptide acids (R,S)‐ 20 and (S,S)‐ 20 , respectively. Coupling of a diastereoisomeric mixture of 20 with H‐Phe‐O^tBu led to the tripeptides 21 (Scheme 5). X‐Ray crystal‐structure determinations of (S,R)‐ 19 and (S,S)‐ 19 allowed the determination of the absolute configurations of all diastereoisomers isolated in this series.     

Controlling Helical Chirality in Atrane Structures: Solvent‐Dependent Chirality Sense in Hemicryptophane‐Oxidovanadium(V) Complexes

The diastereomeric hemicryptophane oxidovanadium(V) complexes (P)‐(S,S,S)‐ 3 and (M)‐(S,S,S)‐ 4 have been synthesized. ¹H and ⁵¹V NMR spectra in solution are consistent with the formation of Λ and Δ forms of the propeller‐like vanatrane moiety, leading to two diastereomeric conformers for each complex: that is, (P)‐(S,S,S‐Λ)‐ 3 /(P)‐(S,S,S‐Δ)‐ 3 and (M)‐(S,S,S‐Λ)‐ 4 /(M)‐(S,S,S‐Δ)‐ 4 . The Λ/Δ ratio is rather temperature‐insensitive but strongly dependent on the solvent (the de of (M)‐(S,S,S)‐ 4 changes from 0 in benzene to 92 % in DMSO). The solvent therefore controls the preferential clockwise or anticlockwise orientation of the propeller‐like atrane unit. The energy barriers for the Λ?Δ equilibrium were determined by NMR experiments, and the highest ΔG^≠ value (103.7 kJ mol^?1) was obtained for (P)‐(S,S,S)‐ 3 , much higher than those reported for other atrane derivatives. This is attributed to the constraints arising from the cage structure. Determination of the activation parameters provides evidence for a concerted, rather than a stepwise, interconversion mechanism with entropies (ΔS^≠) of ?243 and ?272 J mol^?1 K^?1 for (P)‐(S,S,S)‐ 3 and (M)‐(S,S,S)‐ 4 , respectively. The molecular structure of the (P)‐(S,S,S‐Λ)‐ 3 isomer was solved by X‐ray diffraction and shows a distorted structure with one of the linkers located in the CTV cavity. Complementary quantum chemical calculations were carried out to obtain the energy‐minimized structures of (P)‐(S,S,S)‐ 3 and (M)‐(S,S,S)‐ 4 . Our density functional theory calculations suggest that the (P)‐(S,S,S‐Λ)‐ 3 is favored, in agreement with experimental data. For the M series, a similar strategy was used to extract molecular structures and relative energies. As in the case of the P diastereomer, the Λ form dominates over the Δ one.     

Multigram Solution‐Phase Synthesis of Three Diastereomeric Tripeptidic Second‐Generation Dendrons Based on (2S,4S)‐, (2S,4R)‐, and (2R,4S)‐4‐Aminoprolines

Three diastereomeric second‐generation (G2) dendrons were prepared by using (2S,4S)‐, (2S,4R)‐, and (2R,4S)‐4‐aminoprolines on the multigram scale with highly optimized and fully reproducible solution‐phase methods. The peripheral 4‐aminoproline branching units of all the dendrons have the 2S,4S configuration throughout, whereas those units at the focal point have the 2S,4S, 2S,4R, and 2R,4S configurations. These latter configurations led to the dendrons being named (2S,4S)‐ 1 , (2S,4R)‐ 1 , and (2R,4S)‐ 1 , respectively. The 4‐aminoproline derivatives used in this study are new, although many closely related compounds exist. Their syntheses were optimized. The dendron assembly involved amide coupling, the efficiency of which was also optimized by employing the following well‐known reagents: EDC/HOBt, DCC/HOSu, TBTA/HOBt, TBTU/HOBt, BOP/HOBt, pentafluorophenol, and PyBOP/HOBt. It was found that the use of PyBOP is by far the best for dendrons (2S,4S)‐ 1 and (2R,4S)‐ 1 , and pentafluorophenol active ester is best for (2S,4R)‐ 1 . Because of their multigram scale, all couplings were done in solution instead of by solid‐phase procedures. Purifications were, nevertheless, easy. The optical purities of the key intermediates as well as the three G2 dendrons were analyzed by chiral HPLC analysis. These novel, diastereomeric second‐generation dendrons have a rather compact and conformationally highly rigid structure that makes them interesting candidates for applications, for example, in the field of dendronized polymers and in organocatalysis.     

The absolute configuration of 1‐epialexine hemihydrate

The absolute and relative configurations of 1‐epialexine are established by X‐ray crystallographic analysis, giving (1S,2R,3R,7S,7aS)‐1,2,7‐trihydroxy‐3‐(hydroxymethyl)pyrrolizidine. The compound crystallizes as the hemihydrate C₈H₁₅NO₄·0.5H₂O, with hydrogen bonds holding the water molecule in a hydrophilic pocket between epialexine bilayers. In addition, a comparison was made between results obtained from examination of the Bijvoet pairs from data sets collected using molybdenum and copper radiation.     

One‐Handed Helical Screw Direction of Homopeptide Foldamer Exclusively Induced by Cyclic α‐Amino Acid Side‐Chain Chiral Centers

Chiral cyclic α,α‐disubstituted amino acids, (3S,4S)‐ and (3R,4R)‐1‐amino‐3,4‐(dialkoxy)cyclopentanecarboxylic acids ((S,S)‐ and (R,R)‐Ac₅c^dOR; R: methyl, methoxymethyl), were synthesized from dimethyl L ‐(+)‐ or D ‐(?)‐tartrate, and their homochiral homoligomers were prepared by solution‐phase methods. The preferred secondary structure of the (S,S)‐Ac₅c^dOMe hexapeptide was a left‐handed (M) 3₁₀ helix, whereas those of the (S,S)‐Ac₅c^dOMe octa‐ and decapeptides were left‐handed (M) α helices, both in solution and in the crystal state. The octa‐ and decapeptides can be well dissolved in pure water and are more α helical in water than in 2,2,2‐trifluoroethanol solution. The left‐handed (M) helices of the (S,S)‐Ac₅c^dOMe homochiral homopeptides were exclusively controlled by the side‐chain chiral centers, because the cyclic amino acid (S,S)‐Ac₅c^dOMe does not have an α‐carbon chiral center but has side‐chain γ‐carbon chiral centers.     

Metabolism of Deuterated threo‐Dihydroxy Fatty Acids in Saccharomyces cerevisiae: Enantioselective Formation and Characterization of Hydroxylactones and γ‐Lactones

Biotransformation of (±)‐threo‐7,8‐dihydroxy(7,8‐²H₂)tetradecanoic acids (threo‐(7,8‐²H₂)‐ 3 ) in Saccharomyces cerevisiae afforded 5,6‐dihydroxy(5,6‐²H₂)dodecanoic acids (threo‐(5,6‐²H₂)‐ 4 ), which were converted to (5S,6S)‐6‐hydroxy(5,6‐²H₂)dodecano‐5‐lactone ((5S,6S)‐(5,6‐²H₂)‐ 7 ) with 80% e.e. and (5S,6S)‐5‐hydroxy(5,6‐²H₂)dodecano‐6‐lactone ((5S,6S)‐5,6‐²H₂)‐ 8 ). Further β‐oxidation of threo‐(5,6‐²H₂)‐ 4 yielded 3,4‐dihydroxy(3,4‐²H₂)decanoic acids (threo‐(3,4‐²H₂)‐ 5 ), which were converted to (3R,4R)‐3‐hydroxy(3,4‐²H₂)decano‐4‐lactone ((3R,4R)‐ 9 ) with 44% e.e. and converted to ²H‐labeled decano‐4‐lactones ((4R)‐(3‐²H₁)‐ and (4R)‐(2,3‐²H₂)‐ 6 ) with 96% e.e. These results were confirmed by experiments in which (±)‐threo‐3,4‐dihydroxy(3,4‐²H₂)decanoic acids (threo‐(3,4‐²H₂)‐ 5 ) were incubated with yeast. From incubations of methyl (5S,6S)‐ and (5R,6R)‐5,6‐dihydroxy(5,6‐²H₂)dodecanoates ((5S,6S)‐ and (5R,6R)‐(5,6‐²H₂)‐ 4a ), the (5S,6S)‐enantiomer was identified as the precursor of (4R)‐(3‐²H₁)‐ and (2,3‐²H₂)‐ 6 ). Therefore, (4R)‐ 6 is synthesized from (3S,4S)‐ 5 by an oxidation/keto acid reduction pathway involving hydrogen transfer from C(4) to C(2). In an analogous experiment, methyl (9S,10S)‐9,10‐dihydroxyoctadecanoate ((9S,10S)‐ 10a ) was metabolized to (3S,4S)‐3,4‐dihydroxydodecanoic acid ((3S,4S)‐ 15 ) and converted to (4R)‐dodecano‐4‐lactone ((4R)‐ 18 ).     

A New‐Skeleton Diterpenoid,New Prenylbisabolanes,and Their Putative Biogenetic Precursor,from the Red Seaweed Laurencia microcladia from Il Rogiolo: Assigning the Absolute Configuration when Two Chiral Halves are Connected By Single Bonds

We report here a new‐skeleton tricyclic diterpenoid, neorogioldiol ( 8 ), along with new prenylbisabolanes, rogioldiol D ( 6 ) and O¹¹,15‐cyclo‐14‐bromo‐14,15‐dihydrorogiol‐3,11‐diol ( 5 ), and their putative biogenetic precursor, (−)‐geranyllinalool ( 7 ), isolated from the red seaweed Laurencia microcladia, which has colonized a small tract of the Tuscany coast called Il Rogiolo. In a case study of the assignment of the absolute configuration for molecules composed of chiral halves that are connected by single bonds, the absolute configuration of neorogioldiol ( 8 ) was based on a) the assumption of the identity of the cyclohexane moiety with co‐occurring (2S,3R,6S)‐rogiolal ( 4 ) and b) NMR‐derived relative configurations for the bicyclic moiety, and c) the combination of these two pieces of information by molecular‐mechanics‐aided conformational analysis, in agreement with NOE data.