化学酶法合成光学纯亮氨酸

用化学酶法合成L-亮氨酸，先在PdCl2/PPh3/LiBr/H2SO4催化体系作用下，异戊醛酰胺羰基化合成消旋的N-乙酰基亮氨酸；然后在酰基转移酶催化下水解，得到L-亮氨酸和N-乙酰基-D-亮氨酸．文中对酰胺羰基化反应条件进行了优化，分离得到消旋N-乙酰基亮氨酸产率为66．4％．经酶对映选择地水解后得L-亮氨酸，产率为41％，产物L-亮氨酸经衍生化后由气相色谱测定其光学纯度达99％ee．     

光学纯Communesin F中间体的合成

以communesin F消旋体的全合成过程中的醛中间体为原料,在光学纯叔丁基亚磺酰胺的手性诱导下,通过加成和还原反应制得摩尔比为1:1的非对应异构体3a和3b;脱去3a的叔丁基亚磺酰基制得光学纯4; 4的氨基用Boc保护合成了光学纯Communesin F的重要中间体5.3～5的结构经1H NMR表征.     

α-葡萄糖苷酶抑制剂Radicamine B的合成

以D-阿拉伯糖为原料,依次合成了中间体(2R,3R,4R)-2,3,5-三-O-苄氧基-4-羟基-O-叔丁基二甲基硅基-戊醛肟(3),(2R,3S,4S)-2,3,5-三-O-苄氧基-4-碘-O-叔丁基二甲基硅基-戊醛肟(4)和(2R,3R,4R)-3,4-二-O-苄氧基-2-(苄氧甲基)-3,4-二氢-2H-吡咯-1-醇(5);5与芳基Grignard试剂进行高立体选择性的加成反应制得(2R,3R,4R,5R)-3,4-二-O-苄氧基-2-[4-(苄氧基)苯基)]-5-吡咯-1-醇(6);6经催化氢化合成Radicamine B,总收率18.5%。3和4为新化合物,其结构经1HNMR,MS和元素分析表征。     

α-葡萄糖苷酶抑制剂Radicamine A的合成

天然产物Radicamines A和B是日本植物学家Kusano等从半边莲中分离到的两个新型吡咯烷型生物碱,发现它们是有效的α-葡萄糖苷酶抑制剂,根据各种光谱数据推断它们为全反式取代的吡咯烷结构,绝对构型为(2S,3S,4S,5S) [1].后来,本课题组[2]和其它课题组[3,4]分别采用不同的全合成方法纠正了Radicamines A和B的构型,确定其为(2R,3R,4R,5R)(图1).去年,另一课题组采用与我们相似的合成路线率先报道了Radicamines A和B的合成及其对三种糖苷酶的活性研究[5].     

α-萘甲醇衍生物的选择性氧化及手性联萘二酸的合成

α-萘甲醇衍生物与负载型氧化剂A(KMnO4/CuSO4.5H2O)反应,得到相应的醛(酮),产率68%~98%。光学纯的(S)-联萘二醇经A氧化制得光学纯的(S)-联萘二醛;醛经MnO2再次氧化合成了(S)-联萘二酸二甲酯;酯水解得到光学纯的(S)-联萘二酸。     

一种用于合成光学纯联二萘酚的新型催化体系

(S)-二苯基-(α-吡咯烷基)甲醇与氯化亚铜的配合物作为手性催化剂用于2-萘酚及其衍生物的不对称催化氧化偶联反应,产率44.0%,e.e.值50.4%。     

光学纯SunPhos手性双膦烷的合成及其与丙烯酸甲酯的反应

SunPhos 双膦烷可以用氢化铝锂和三甲基氯硅烷还原相应的光学纯的双磷酸酯获得，该双膦烷和丙烯酸甲酯反应，可得膦烷被双烷基化的富电子膦配体。     

合成光学活性樟脑

目前按所谓“四步法”生产的合成樟脑是消旋的。天然樟脑是光学活性的,大多数为右旋体。左旋天然樟脑较为稀少。藤原羲人,松原羲治等曾报道合成光学活性樟脑,其中龙脑脱氢反应是在有机溶剂的存在下进行的,产物的光学纯度为原料的70%左右。     

光催化氧化还原体系中硝酮与芳香叔胺的自由基偶联反应

通过氮α-位碳自由基构造氮α-位碳-碳键是合成含氮有机化合物的重要方法. 近期, 利用可见光催化氧化芳香叔胺—氮α-位去质子化形成氮α-位碳自由基的原理发展了一系列新颖的自由基加成(偶联)反应, 成为氮α-位碳自由基化学发展的重要方向. 本文应用Ir-催化剂, 实现了光催化氧化还原体系中硝酮与芳香叔胺的自由基偶联反应, 高效地合成β-氨基羟胺化合物. 该反应条件温和、操作简单, 具有较高的原子经济性, 且对于各种链状、环状以及手性硝酮都具有良好的适用性, 产物可方便地转化为重要的邻二胺化合物.     

Synthesis of Cyclic Vicinal Trifluoromethylated Hydroxylamine and Nitrone Based on Perfluorodiacetyl

Perfluorodiacetyl (PFDA) demonstrates high‐synthetic potential in reaction with bifunctional nucleophilic reagents. Therefore, PFDA is a useful reagent in the synthesis of CF₃‐substituted heterocycles. In this work, we explored the reaction of PFDA with a sterically hindered bis‐hydroxylamine, isolated the products and clarified their structures. It was found that the reaction initially gave the 5,5,6,6‐tetramethyl‐2,3‐bis(trifluoromethyl)pyperazine‐1,2,3,4‐tetraol heterocycle with a unique set of functional groups. This tetraol was shown to easily undergo dehydration with formation of the first cyclic α‐CF₃‐substituted nitrone.     

Synthesis of Alkanophosphonates Containing Nitrone Moiety

Abstract

α-Phosphonylonitrones are relatively new class of phospho- roorganic compounds ^1,2. Nitrones 2 are especially interesting due to the possibility of their conversion to amino-alkanephosphonates. In this communication we would like to present some results on the synthesis of α-N-alkylnitro-noδ-alkanophosphonates 2 and their conversion to the corresponding isoxazolidines 3 ³.     

Synthesis of an L-Fucose-Derived Cyclic Nitrone and its Conversion to α-L-Fucosidase Inhibitors

The L -fuco-nitrone 1 has been synthesized from allyl 4,6-O-benzylidene-α-D -glucopyranoside ( 4 ) in 11 steps and an overall yield of 18%. The key step is the intramolecular alkylation of an intermediary 1,1-bis(hydroxylamine) derived from the tosyloxy oximes (E/Z)- 2 . The nitrone 1 has been transformed into the diamine 30 , the indolizidines 39 and 40 , the indolizidinones 34 and 35 , and the imidazole 44 , all inhibiting bovine epididymis α-L -fucosidase with IC₅₀ values between 105 nM and 240 μM .     

Synthesis of Biaryl-Bridged Cyclic Peptides via Catalytic Oxidative Cross-Coupling Reactions

Biaryl-bridged cyclic peptides comprise an intriguing class of structurally diverse natural products with significant biological activity. Especially noteworthy are the antibiotics arylomycin and its synthetic analogue G0775, which exhibits potent activity against Gram-negative bacteria. Herein, we present a simple, flexible, and reliable strategy based on activating-group-assisted catalytic oxidative coupling for assembling biaryl-bridged cyclic peptides from natural amino acids. The synthetic approach was utilized for preparing a number of natural and unnatural biaryl-bridged cyclic peptides, including arylomycin/G0775 and RP 66453 cyclic cores.     

Synthesis of Enantiopure N-tert-Butoxycarbonyl-2-aminocycloalkanones

A route to enantiomerically pure N-tert-butoxycarbonyl-2-aminocycloalkanones (ring size: 5-8 membered) from the corresponding cycloalkene oxides is described. The procedure involves (1) aminolysis with (S)-α-methylbenzylamine/Me₃A1 and chromatographic separation of diastereomers, (2) hydrogenolysis to afford the trans-2-aminocycloalkanols, (3) tert-butoxycarbonyl (Boc) protection, and (4) PCC oxidation.     

Synthesis of Enantiopure Chiral Perhydrobenzimidazole and Hexahydroquinoxaline Derivatives

 Starting from 2-anilino-2-ethoxy-3-oxothiobutyric acid anilides and (R, R)-or (S, S)-trans-1,2-diaminocyclohexane, chiral C2-disubstituted perhydrobenzimidazole and trans-4a,5,6,7,8,8a-hexahydroquinoxaline derivatives were obtained depending on the polarity of the solvent.     

Synthesis of Enantiopure Chiral Perhydrobenzimidazole and Hexahydroquinoxaline Derivatives

Summary.  Starting from 2-anilino-2-ethoxy-3-oxothiobutyric acid anilides and (R, R)-or (S, S)-trans-1,2-diaminocyclohexane, chiral C2-disubstituted perhydrobenzimidazole and trans-4a,5,6,7,8,8a-hexahydroquinoxaline derivatives were obtained depending on the polarity of the solvent. Received April 10, 2000. Accepted May 2, 2000