The First Total Synthesis of Various Thiostrepton-type Macrocyclic Antibiotics and the Structure-Bioactivity Relationship.

多种硫链丝菌素类大环抗生素的首次全合成及其构效关系。

• 批准号: 14550829
• 负责人: SHIN Chung-gi
• 金额: $ 2.37万
• 依托单位: Kanagawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14550829/
• 关键词: Thiostrepton antibiotics; Thiocillins I; Sulfomycins; Cyclochiazomycin; Dehydrooligopeptide; Total synthesis; 2,3,5-Tristhiazolyl pyridine.; Dehydrothiazole amino acid.; Dehydrooxazole amino acid.; ビストラタミド; スロホマイシン; ベルニナマイシン; テロメスタチン

Recently, many thiostrepton-type macrocyclic antibiotics, such as micrococcin P and P_1, and GE 2270 A, have been isolated from various secondary metabolites of Buchillus pumilus and Planobispola rose, respectively. The natural products exhibit very interesting bioactivities, such as antitumor and antibacterial activities, and include a characteristic main structure, in common 2,3,6-tristhiazolyl-substituted pyridine skeleton called Fragment A-C constructed of a polythiazole pyridine segment [Fragment A] and thiazolyl side chain called Fragment C. Furthermore, a unique polysubstitutedthiazole segment called Fragment B as a substructure. The total syntheses of the above mentioned antibiotics have been already accomplished by us. Here, similarly to the cases of the micrococcins P, P_1 and GE 2270 A, the first total synthesis of thiocilline I and convenient synthesis of the Fragment B-C of sulfomycin I, isolated from Bucillus bodius and Streptomyces viridchromogenes MCRL-0368 respectively, have been also achieved, after syntheses of he each Fragments A, B, and C, and then fragment condensations. These results will certainly contribute to the total synthesis of other similar thiostrepton-type antibiotics.

近年来，从短小芽孢杆菌和Planobispola rose的次级代谢产物中分离出了许多硫链丝菌素类大环抗生素，如微球菌素P和P_1，以及GE 2270 A。天然产物显示出非常令人感兴趣的生物活性，例如抗肿瘤和抗菌活性，并且包括特征性的主结构，在共同的2，3，6-三噻唑基取代的吡啶骨架中，称为片段A-C，其由聚噻唑吡啶片段[片段A]和称为片段C的噻唑基侧链构成。此外，一个独特的多取代噻唑片段称为片段B作为亚结构。我们已经完成了上述抗生素的全合成。与微球菌P、P_1和GE 2270 A的情况类似，在合成片段A、B和C，然后进行片段缩合之后，也实现了硫代西林I的首次全合成和分别从Bucillus bodius和Streptomyces viridchromogenes MCRL-0368分离的磺霉素I的片段B-C的方便合成。这些结果必将有助于其他类似硫链丝菌素类抗生素的全合成。

项目成果

C.Shin, Y.Yonezawa, et al.: "Convenient Synthesis of the Main Tridehydropentapeptide Skeleton for a Macrocyclic Antibiotic, Sulfomycin I."Chem.Lett.. 33. 72-73 (2004)

C.Shin、Y.Yonezawa 等人：“大环抗生素磺霉素 I 的主要三脱氢五肽骨架的便捷合成”Chem.Lett.. 33. 72-73 (2004)

辛 重基(分担執筆): "プロティンエンジニアリングの基礎(普及版)"シーエムシー. 350 (2003)

Chung-ki Shin（撰稿人）：“蛋白质工程基础（通俗版）”CMC 350（2003）。

T.Kayano, Y.Yonezawa, C.Shin: "Convenient Synthesis of the Main Tridehydropentapeptide Skeleton for a Macrocyclic Antibiotic, Sulfomycin I"Chem.Lett.. 33. 72-73 (2004)

T.Kayano、Y.Yonezawa、C.Shin：“大环抗生素磺霉素 I 的主要三脱氢五肽骨架的便捷合成”Chem.Lett.. 33. 72-73 (2004)

N.Endoh, K.Tsuboi, R.Kim, Y.Yasuchika, C.Shin: "Useful Synthesis of the Longer Array Oxazole Rings for Telomestatin"Heterocycles. 60. 1567-1572 (2003)

N.Endoh、K.Tsuboi、R.Kim、Y.Yasuchika、C.Shin：“用于端美他汀的较长阵列恶唑环的有用合成”杂环。

Y.Yonezawa, C.Shin, et al.: "A Synthesis of a Hydroxyvaline-derived Thiazole-4-carboxylate Constituting an Antibiotic, Thiocilline I."Heterocycles. 57. 903-908 (2002)

Y.Yonezawa、C.Shin 等人：“构成抗生素硫青霉素 I 的羟缬氨酸衍生的噻唑-4-羧酸盐的合成”。杂环。