(3S,9S,12R,16S)-6-eth-(Z)-ylidene-3,12-diisopropyl-16-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone | 180973-35-7

分子结构分类

有机化合物 - 有机酸及其衍生物 - 肽模拟物

中文名称

——

中文别名

——

英文名称

(3S,9S,12R,16S)-6-eth-(Z)-ylidene-3,12-diisopropyl-16-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone

英文别名

(3S,9S,12R,16S,E)-6-ethylidene-3,12-diisopropyl-16-[(E)-4-(tritylthio)but-1-enyl]-9-(tritylthiomethyl)-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone；(3S,6Z,9S,12R,16S)-6-ethylidene-3,12-di(propan-2-yl)-16-[(E)-4-tritylsulfanylbut-1-enyl]-9-(tritylsulfanylmethyl)-1-oxa-4,7,10,13-tetrazacyclohexadecane-2,5,8,11,14-pentone

(3S,9S,12R,16S)-6-eth-(Z)-ylidene-3,12-diisopropyl-16-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone化学式

CAS

180973-35-7

化学式

C₆₂H₆₆N₄O₆S₂

mdl

——

分子量

1027.36

InChiKey

YALWISFBODJUKT-DIUKBXQUSA-N

BEILSTEIN

——

EINECS

——

物化性质

沸点：

1151.2±65.0 °C(Predicted)
密度：

1.177±0.06 g/cm3(Predicted)

计算性质

辛醇/水分配系数(LogP)：

12.3
重原子数：

74
可旋转键数：

16
环数：

7.0
sp3杂化的碳原子比例：

0.27
拓扑面积：

193
氢给体数：

4
氢受体数：

8

上下游信息

上游原料

中文名称	英文名称	CAS号	化学式	分子量
——	(3S,6S,12S,15R,Z)-15-amino-9-ethylidene-6-isopropyl-16-methyl-5,8,11,14-tetraoxo-3-((E)-4-(tritylthio)but-1-en-1-yl)-12-((triphenylmethylthio)methyl)-4-oxa-7,10,13-triazaheptadecan-1-oic acid	——	C₆₂H₆₈N₄O₇S₂	1045.38
——	(5E,7R,11R,14S,17E,20S)-methyl 17-ethylidene-7-hydroxy-11,20-diisopropyl-9,12,15,18-tetraoxo-1,1,1-triphenyl-14-(tritylthiomethyl)-2-thia-10,13,16,19-tetraazahenicos-5-en-21-oate	181141-24-2	C₆₃H₇₀N₄O₇S₂	1059.4
——	(5E,7S,11R,14S,17E,20S)-methyl 17-ethylidene-7-hydroxy-11,20-diisopropyl-9,12,15,18-tetraoxo-1,1,1-triphenyl-14-(tritylthiomethyl)-2-thia-10,13,16,19-tetraazahenicos-5-en-21-oate	180973-33-5	C₆₃H₇₀N₄O₇S₂	1059.4
——	(5E,7S,11R,14S,17E,20S)-17-ethylidene-7-hydroxy-11,20-diisopropyl-9,12,15,18-tetraoxo-1,1,1-triphenyl-14-(tritylthiomethyl)-2-thia-10,13,16,19-tetraazahenicos-5-en-21-oic acid	180973-34-6	C₆₂H₆₈N₄O₇S₂	1045.38
——	(5E,7R,11R,14S,17E,20S)-17-ethylidene-7-hydroxy-11,20-diisopropyl-9,12,15,18-tetraoxo-1,1,1-triphenyl-14-(tritylthiomethyl)-2-thia-10,13,16,19-tetraazahenicos-5-en-21-oic acid	181141-25-3	C₆₂H₆₈N₄O₇S₂	1045.38
——	methyl (2S)-2-[[(Z)-2-[[(2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-3-tritylsulfanylpropanoyl]amino]but-2-enoyl]amino]-3-methylbutanoate	180973-32-4	C₃₇H₄₆N₄O₅S	658.862
——	(S)-2-((2S,3R)-2-{(S)-2-[(R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-methyl-butyrylamino]-3-tritylsulfanyl-propionylamino}-3-hydroxy-butyrylamino)-3-methyl-butyric acid methyl ester	180973-30-2	C₅₂H₅₈N₄O₈S	899.121
——	(S)-2-{(2S,3R)-2-[(S)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-tritylsulfanyl-propionylamino]-3-hydroxy-butyrylamino}-3-methyl-butyric acid methyl ester	180973-28-8	C₄₇H₄₉N₃O₇S	799.988
——	methyl N-(N-((((9H-fluoren-9-yl)methoxy)carbonyl)-D-valyl)-S-trityl-D-cysteinyl)-O-tosyl-L-threonyl-L-valinate	180973-31-3	C₅₉H₆₄N₄O₁₀S₂	1053.31

下游产品

中文名称	英文名称	CAS号	化学式	分子量
——	romidepsin	128517-07-7	C₂₄H₃₆N₄O₆S₂	540.705
——	7-Ethylidene-4,21-di(propan-2-yl)-2-oxa-12,13-dithia-5,8,20,23-tetrazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone	128517-07-7	C₂₄H₃₆N₄O₆S₂	540.7

反应信息

作为反应物：

描述：

(3S,9S,12R,16S)-6-eth-(Z)-ylidene-3,12-diisopropyl-16-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone 在碘作用下，以甲醇、二氯甲烷为溶剂，反应 0.33h，以75%的产率得到romidepsin

参考文献：

名称：

双环二肽HDAC抑制剂Spichochostatins A和B，5''-epi-Spiruchostatin B，FK228（FR901228）的全合成及其生物学活性的初步评估

摘要：

双环去肽肽组蛋白去乙酰化酶（HDAC）抑制剂spiruchostatins A和B，5'′- epi- spiruchostatin B和FK228可以通过聚合和统一的方式高效合成。合成方法涉及以下关键步骤：i）1，3-丙二醇衍生的砜和L-或D-苹果酸衍生的醛的Julia-Kocienski烯化反应，以合成最具挑战性的单元（3 S或3 R，4 E）-3-羟基-7-巯基庚基-4-烯酸，存在于含有D-丙氨酸或D-缬氨酸的链段中；ii）D-缬氨酸-D-半胱氨酸-或D的缩合-同种异体-isoleucine- d -半胱氨酸含与段d -alanine-或d含缬氨酸段直接组装相应的开环-acids; 和iii）的大环化开环使用椎名法或光延法构造必需15-或16-元大环内酯-酸。本合成已建立了螺旋藻抑素B的C5'立体化学。此外，对合成的二肽的HDAC抑制测定和细胞生长抑制分析确定了其效力的顺序，并揭示了

DOI：

10.1002/chem.200901552
作为产物：

描述：

三苯甲硫醇在 Ti(IV) complex with (S)-(-)-binaphthyl amino alcohol 4-二甲氨基吡啶、 lithium hydroxide 、草酰氯、二异丁基氢化铝、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 caesium carbonate 、对甲苯磺酸、二甲基亚砜、盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺、三乙胺、 N,N-二异丙基乙胺作用下，以甲醇、水为溶剂，生成 (3S,9S,12R,16S)-6-eth-(Z)-ylidene-3,12-diisopropyl-16-((E)-4-tritylsulfanyl-but-1-enyl)-9-tritylsulfanylmethyl-1-oxa-4,7,10,13-tetraazacyclohexadecane-2,5,8,11,14-pentaone

参考文献：

名称：

Total Synthesis of the Antitumor Depsipeptide FR-901,228

摘要：

DOI：

10.1021/ja9613724

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文献信息

Process for the preparation of (1S, 4S, 7Z, 10S, 16E, 21R)-7-ethyldene-4,21-bis(1-methyl-ethyl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8.7.6]tricos-16-ene-3, 6, 9, 19, 22-pentone

申请人：Rajan Srinivasan Thirumalai

公开号：US10562931B2

公开（公告）日：2020-02-18

The present invention is relates to an improved process for the preparation (1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-bis(1-methylethyl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabi-cyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone of formula I.

本发明涉及一种制备式 I 的(1S,4S,7Z,10S,16E,21R)-7-亚乙基-4,21-双(1-甲基乙基)-2-氧杂-12,13-二硫杂-5,8,20,23-四氮杂双环[8.7.6]三os-16-烯-3,6,9,19,22-戊酮的改进工艺。
Macrolactamization versus Macrolactonization: Total Synthesis of FK228, the Depsipeptide Histone Deacetylase Inhibitor

作者：Shijun Wen、Graham Packham、A. Ganesan

DOI：10.1021/jo801866z

日期：2008.12.5

The cyclic depsipeptide FK228 is the only natural product histone deacetylase (HDAC) inhibitor that has advanced to clinical trials Lis an anticancer agent. While currently obtained by fermentation, total synthesis is in attractive alternative that will facilitate the preparation of unnatural analogues. The previous total syntheses of FK228 featured macrocylization by ester bond formation from a seco-hydroxy acid. Such routes are operationally jeopardized by the steric hindrance of the carboxylic acid and the sensitivity of the allylic alcohol toward elimination. We report a strategically different approach whereby the ester bond is formed intermolecularly at an early stage and macrocyclization is efficiently achieved by amide bond formation.
Improved Total Synthesis of the Potent HDAC Inhibitor FK228 (FR-901228)

作者：Thomas J. Greshock、Deidre M. Johns、Yasuo Noguchi、Robert M. Williams

DOI：10.1021/ol702957z

日期：2008.2.1

A scaleable synthesis of the potent histone deacetylase (HDAC) inhibitor FK228 is described. A reliable strategy for preparing the key,beta-hydroxy mercapto heptenoic acid partner was accomplished in nine steps and 13% overall yield. A Noyori asymmetric hydrogen-transfer reaction established the hydroxyl stereochemistry in >99:1 er via the reduction of a propargylic ketone.
J. Am. Chem. Soc. 1996, 118, 7237-7238

作者：

DOI：——

日期：——