TOTAL SYNTHESIS OF TIRANDAMYCIN AND STREPTOLYDIGIN

泰兰霉素和链霉素的全合成

• 批准号: 3129580
• 负责人: PHILIP Ridley DESHONG
• 金额: $ 9.7万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-03-01 至 1986-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3129580
• 关键词: DNA directed RNA polymerase; anaerobic bacteria; antibacterial agents; antibiotics; antihyperlipoproteinemic agent; antineoplastic antibiotics; drug design /synthesis /production; lymphoblast; nucleotidyltransferase

This proposal outlines a strategy for the total synthesis of tirandamycin and streptolydigin in optically active form. Tirandamycin and Streptolydigin are members of the 3-enoyl tetramic acid family of metabolites isolated from various strains of Streptomyces. Streptolydigin has been shown to selectively inhibit terminal deoxynucleotidyl transferase (TDT), an enzyme present in large quantities in leukemic lymphoblasts, but not in normal leucocytes. TDT is believed to play a crucial role in the cellular metabolism of these cancer cells. It is possible that stretolydigin/tirandamycin or an analogue of these natural products will prove effective in the treatment of various leukemias. Tirandamycin and streptolydigin also display antimicrobial activity by inhibiting bacterial DNA-directed RNA polymerase. These compounds are especially effective in arresting the growth of anaerobic bacteria which are responsible for pelvic and abdominal infections. The synthetic strategy outlined in the proposal would yield optically active tirandamycin or streptolydigin in approximately 20 steps by a convergent route and would have sufficient generality that a diversity of structural analogues could be readily prepared for testing as antileukemic or antimicrobial agents.

该提案概述了蒂兰丹霉素总合成的策略 并以光学活性形式进行链氨二甲。 Tirandamycin和 链氨二基酸是3-烯酰二酰酸家族的成员 从各种链霉菌菌株中分离出来的代谢产物。 链酰二糖 已证明可以选择性抑制末端脱氧核苷酸转移酶 （TDT），一种酶，大量存在于白血病细胞中，但 不在正常的白细胞中。 据信TDT在 这些癌细胞的细胞代谢。 有可能 stretolydigin/tirandamycin或这些天然产品的类似物将 证明有效治疗各种白血病。 Tirandamycin和 链氨二基酸还通过抑制细菌表现出抗菌活性 DNA指导的RNA聚合酶。 这些化合物特别有效 捕捉导致骨盆的厌氧菌的生长 和腹部感染。 提案中概述的合成策略 将在中产生光学活性的tirandamycin或链酚 大约有20个步骤，通过收敛路线，将有足够的路线 一般性的结构类似物可以很容易地很容易 准备作为抗利血症或抗菌剂的测试。

项目成果

Stereoselectivity in the formation of pentacarbonylglycosylmanganese complexes.

五羰基糖基锰络合物形成中的立体选择性。

• DOI: 10.1016/s0008-6215(00)90897-8
• 发表时间: 1987
• 期刊: Carbohydrate research
• 影响因子: 3.1
• 作者: DeShong,P;Slough,GA;Elango,V
• 通讯作者: Elango,V