高效液相色谱法手性拆分(2-戊基-3-苯基-2,3环氧丙烷基)二苯基磷酸酯对映体

采用多糖类手性色谱柱,建立了(2-戊基-3-苯基-2,3环氧丙烷基)二苯基磷酸酯对映体的高效液相色谱手性拆分方法。考察了手性柱类型、流动相组成、流速、柱温等对手性拆分的影响,并对分离机制进行了探讨。结果表明,采用Chiralpak AS-H柱(250×4.6mm,i.d.,5μm),以正己烷-异丙醇(85∶15,V/V)为流动相,在柱温25℃,流速1.0mL/min,检测波长210nm的条件下,(2-戊基-3-苯基-2,3环氧丙烷基)二苯基磷酸酯对映体能达到完全分离,且稳定性和重复性好。该方法也适用于(2-戊基-3-苯基-2,3环氧丙烷基)二苯基磷酸酯类似物的手性拆分。     

(S)-2-乙氧基-3-(4-羟基苯基)丙酸乙酯的合成

(S)-2-乙氧基-3-(4-羟基苯基)丙酸乙酯的合成;二乙氧基乙酸乙酯;Horner Wadswordth Emmons反应;催化氢化;化学拆分;（S） 乙氧基（羟基苯基）     

2,2-二(4-羟基-3-氨基)苯基丙烷的合成

在乙醇介质中,以Fe(OH)3／C为催化剂,用80％水合肼将2,2-二(4-羟基-3-硝基)苯基丙烷还原为2,2-二(4-羟基-3-氨基)苯基丙烷。产率99．0％,纯度98．5％。考察了10种金属离子对催化剂活性的影响,结果发现Pb^2 会引起催化剂中毒;Mg^2 ,Cu^2 和Zn^2 钝化了催化剂的催化活性;Ba^2 和Cr^3 不影响催化剂的活性;Al^3 ,Ni^2 ,Ti^3 和Ti^4 能活化催化剂,使反应速度加快,但它们单独使用时无催化活性。     

二-(2-羟基-5-长链烷基苯基)-甲烷的合成

以脂肪酸、苯酚为原料, 经酰化反应、酯化反应、Fries重排、黄鸣龙还原等步骤, 得到正构长链烷基酚, 再与多聚甲醛在酸性催化剂下进行缩合反应, 生成二-(2-羟基-5-长链烷基苯基)-甲烷, 用核磁共振氢谱和碳谱、红外光谱和元素分析对产物进行了结构鉴定. 据上述反应路线, 以工业品壬基酚和多聚甲醛为原料, 合成出了二-(2-羟基-5-壬基苯基)-甲烷, 并对其工艺条件进行了研究. 结果表明, 选用草酸作催化剂, 烷基酚和甲醛物质的量比为2∶1, 130 ℃反应4 h, 产物产率达到60%, 且反应转化率和选择性分别为63%和95%.     

3-(2-羟基苯基)-5-苯基-6-乙氧羰基-2-环己烯酮的合成与晶体结构

合成了3-(2-羟基苯基)-5-苯基-6-乙氧羰基-2-环己烯酮.通过元素分析、红外光谱、紫外光谱、核磁共振氢谱和质谱对其组成和结构进行了表征.利用X射线衍射分析方法测定了它的晶体结构.该化合物的晶体属单斜晶系,空间群P21/c,a=1.41946(17)nm,b=0.58445(7)nm,c=2.1756(3)nm,β=104.795(2)°,V=1.7450(4)nm3,Z=4,Dc=1.280 g·cm-3,F(000)=712,μ=0.088mm-1,R1[I＞2σ(I)]=0.0627,wR2[I＞2σ(I)]=0.1484.晶体结构测定结果表明化合物分子中的环己烯部分为半椅式构象,分子间通过氢键形成具有16元环的二聚体.     

新型手性N-烷基-3-蒎胺类化合物的合成及其抑菌活性的研究

以(1S,5S)-(－)-α-蒎烯为原料合成了系列新型(1S,2S,3S,5R)-N-烷基-3-蒎胺类化合物. (－)-α-蒎烯经硼氢化氧化、重铬酸吡啶盐(PDC)氧化得到(1S,2S,5R)-(－)-3-蒎酮; 在BF3•(C2H5)2O催化下(1S,2S,5R)-(－)-3-蒎酮与伯胺化合物反应生成Schiff碱, 再经KBH4或NaBH4还原得到(1S,2S,3S,5R)-N-烷基-3-蒎胺类化合物. 采用FT-IR, 1H NMR, 13C NMR和GC-MS等分析手段对合成所得(1S,2S,5R)-N-烷基-3-蒎烷亚胺和(1S,2S,3S,5R)-N-烷基-3-蒎胺类化合物的结构进行了表征. 考察了(1S,2S,3S,5R)-N-烷基-3-蒎胺类化合物对大肠杆菌(E. coli)、金黄色葡萄球菌(S. aureus)、枯草芽胞杆菌(B. subtilis)、荧光假单胞菌(P. fluorescens)、白色念珠菌(C. albicans)、黑曲霉(A. niger)和米根霉(R. oryzae)等细菌和真菌的抑菌和杀菌活性. 结果表明(1S,2S,3S,5R)-N-正庚基-3-蒎胺对真菌和细菌均表现出良好的杀菌和抑菌活性.     

(5S,6R)-2-(4-甲基)苯基-6-[(1R)-叔丁基二甲基硅氧乙基]-青霉烯-3-羧酸乙酯的合成研究

青霉烯[1]类抗生素是近年来发展很快的一种非典型β-内酰胺抗生素.青霉烯类化合物[2]具有广泛的抗菌活性,具有优于碳青霉烯类抗生素的特点,其固体化合物和酯型前药可口服吸收,不易被β-内酰胺酶水解,同时对脱氢肽水解酶-I( DHP-I )较碳青霉烯稳定.     

(R,S)-α-羟基苯丁酸乙酯的HPLC手性分离

建立了手性柱HPLC法测定盐酸贝那普利的中间体(R)-α-羟基苯丁酸乙酯中的(S)-α-羟基苯丁酸乙酯。采用Chiralcel OD-H色谱柱,流动相正己烷-异丙醇（体积比90：10),流速1．0mL／min,检测波长254nm,进样体积20μL,按外标法以峰面积计算(R)-α-羟基苯丁酸乙酯中的(S)-α-羟基苯丁酸乙酯的含量。(S)体的线性范围5．5～23．8μg／mL,检出限0．47μg／mL(S／N=3),回收率为96％～103％,精密度RSD为2．1％(n=6)。     

Synthesis and Absolute Configuration of (2S,3S,3aS,6S,7aR)-2,3-Dihydroxy-2-((R)-1-hydroxy-3-methylbutyl)-3,6-dimethylhexahydrobenzofuran-4(2H)-one

To investigate the anti-ulcer effect of bisabolangelone reduction derivatives, the sesquiterpene was further proceeded with dihydroxylation reaction. The structure of the target compound was characterized by IR, ESI-MS, 2D NMR and elemental analysis, and its absolute configuration was confirmed with a Flack parameter of 0.08(16) by X-ray crystallography using a Cu radiation source. Compound(3), C_(15)H_(26)O_5, crystal data: monoclinic system, space group P2_1, a = 11.467(2), b = 6.0303(12), c = 11.711(2) ?, β = 99.70(3)°, V = 798.3(3) ?~3, Z = 2, F(000) = 312, D_c = 1.191 g/cm~3, μ = 0.723 mm~(-1), R = 0.0303 and wR = 0.0797 for 2590 independent reflections(Rint = 0.0164) and 2563 observed ones(I 2σ(I)).     

Preparation of Enantiomerically Enriched (2R,3R)- or (2S,3S)-trans-2,3-Diaryloxiranes via Camphor-Derived Sulfonium Ylides

Easily available D-(+)-camphor-derived sulfides 3, 4, 6, and 7 were employed for enantioselective epoxidation via an ylide route. When benzylated or methylated sulfides were used as reagents or mediators for benzylidene transfer, stoichiometric and catalytic epoxidations were realized, respectively. Opposite asymmetric induction was achieved only when sulfides containing exo- (3 and 4) and endo- (6 and 7) alkylthio groups were used. That is, both (+)- and (-)-trans-diaryloxiranes could be obtained in excellent yields and moderate to good ee values under extremely mild conditions from the same chiral pool-derived reagents. A nonbonded interaction between the free OH in the ylides from sulfides (3, 6, and 7) and the carbonyl group of aldehydes controls the approach of the substrates to the ylidic carbon preferentially at one specified face and therefore leads to a more efficient asymmetric induction than that in the case of the ylide from methyl-protected hydroxylated sulfides 4, which cannot cause such an interaction. The same opposite asymmetric induction was also observed in the catalytic reaction with methyl-protected hydroxylated sulfide 4b and unprotected hydroxylated sulfide 3b.     

(R,R)-2,3-Butanediol and (s)-pinanediol allylboronates in chiral synthesis of (2S,3S)-3-methyl-5-hexen-2-ol

(R,R)-Butanediol (dichloromethyl)boronate ( 1 ) with 1 equiv. allylmagnesium halide yields (R,R)-2,3-butanediol (1S)-(1-chloro-3-butenyl)boronate ( 3 ) together with the diallylated product (R,R)-2,3-butanediol (1-allyl-3-butenyl)boronate ( 4 ). The formation of 4 is unprecedented in reactions of α-chloroboronic esters with Grignard reagents. With methylmagnesium bromide 3 yielded (R,R)-2,3-butanediol (1S)-(1-methyl-3-butenyl)boronate ( 5 ), which failed to hydrolyze with water. Hydrolysis of 3 yielded impure α-chloroboronic acid, which was esterified with pinacol and treated with methylmagnesium bromide to form 6 , which with (dichloromethyl)lithium followed by methylmagnesium bromide yielded diastereomeric boronic esters 7 and 8 . Oxidation by hydrogen peroxide yielded (2S,3S)- and (2R,3S)-3-methyl-5-hexen-2-ol ( 9 and 10 , ees unknown). Treatment of (s)-pinanediol allylboronate ( 11 ) with (dichloromethyl)lithium at −100°C followed by zinc chloride at up to 25°C has proceeded in the normal way to form (s)-pinanediol (1S)-(1-chloro-3-butenyl)-boronate ( 12 ), which has been elaborated via 13 , 14 , and 15 to (2S,3S)-3-methyl-5-hexen-2-ol ( 9 ) in 95% de.