Total synthesis of Macrocyclic Thiopeptide Antibiotic Constructing Ployheterocyclic Compounds and Unusual Amino Acids

The total syntheses of macrocyclic antibiotics， micrococcins P and PイイD21イエD2 （1，2）， were first achieved。这些抗生素具有独特的结构，由四个成分组成，称为碎片A、B、C和D。在具体情况下，中央吡啶酮（片段A）和外环侧链（片段D）的结构1和2彼此略有不同。第一，在构建中心2、3、6-三氮唑基替代的吡啶酮之后（片段A-C段） （4）来自乙基2-（2-溴乙酰基-6-二羟甲基-3-吡咯烷基）-噻唑-4-羧化（3）在11个步骤中，含2-（Z）-1的4的成功片段条件（O-t-butyldiphenylsilyl-L-三聚氰胺）-1-丙硫唑-4-羧化和（S）-1-（O-methoxymethyl-L-threoylamino）-2-（O-methoxymethyl）-2-丙醇（5） （受保护的片段B和C moieties， Respectively）给予受保护的片段A-B-C-D段6。用三氟乙酸酸对所有保护组的6种进行次级保护，然后用BOP作为一种在预期的微可卡因P （1）下使用高稀释剂的条件，Furthermore，通过合成方法的各种化学修改，2种合成方法的总合成方法也是第一次完成的。合成物1和2是固有的，与自然1和2对化学和物理特性的尊重。

The total syntheses of macrocyclic antibiotics, micrococcins P and PィイD21ィエD2 (1,2), were first achieved. These antibiotics have unique structures and are constructed of four components called Fragments A, B, C, and D. In particular, the structures of the central pyridine skeleton(Fragment A) and the exocyclic side-chain(Fragment D) of 1 and 2 are slightly different each other. First of all, after constructing the central 2, 3, 6-tristhiazolylsubstituted pyridine skeleton(Fragment A-C segment) (4) from ethyl 2-(2-bromoacetyl-6-dimethoxymethyl-3-pyridyl)-thiazole-4-carboxylate (3) in 11 steps, successive fragment condensations of 4 with ethyl 2-(Z)-1(O-t-butyldiphenylsilyl-L-threoylamino)-1-propenylthiazole-4-carboxylate and (S)-1-(O-methoxymethyl-L-threoylamino)-2-(O-methoxymethyl)-2-propanol (5) (the protected Fragment B and C moieties, respectively) gave the protected Fragment A-B-C-D segment 6. Subsequent deprotecting of all the protecting groups of 6 with trifluoroacetic acid and then cyclization by using BOP as condensing agent under high dilution gave the expected micrococcin P (1).Furthermore, by various chemical modifications of the synthetic method for 1, the total synthesis of 2 was also first accomplished. The synthetic 1 and 2 were identical with the natural 1 and 2 with respect to the chemical and physical properties.