- AN IMPROVED PROCESS FOR THE PREPARATION OF (1S, 4S, 7Z, 10S, 16E, 21R)- 7-ETHYLIDENE-4,21-BIS(1-METHYLETHYL)-2-OXA-12,13-DITHIA-5, 8, 20, 23- TETRAAZABICYCLO[8.7.6]TRICOS-16-ENE-3, 6, 9, 19, 22-PENTONE
-
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.
- -
-
Page/Page column 24
(2017/05/19)
-
- Study for diastereoselective aldol reaction in flow: synthesis of (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid, a key component of cyclodepsipeptide HDAC inhibitors
-
Abstract Flow synthesis of (E)-(S)-3-hydroxy-7-tritylthio-4-heptenoic acid (5), a key component of cyclodepsipeptide histone deacetylase inhibitors was achieved. An efficient flow system for the synthesis of α, β-unsaturated ester 8 was established using a flow reactor column packed with polymer-supported 1,4-diazabicyclo[2.2.2]octane and a fast mixing accessible flow reactor (Comet X-01). Enal 9 was efficiently prepared by a partial reduction of the α, β-unsaturated ester 8 using diisobutylaluminium hydride in the flow system, and the continuous-flow diastereoselective aldol reaction was performed at low temperature, giving a good yield and diastereoselectivity of the desired aldol 10.
- Doi, Takayuki,Otaka, Hiroyuki,Umeda, Koji,Yoshida, Masahito
-
p. 6463 - 6470
(2015/08/18)
-
- Depsipeptides and Their Therapeutic Use
-
A Compound of structure (IX) or (X) or a pharmaceutically acceptable salt thereof, wherein: X is —C(═O)N(R10)— or —CH(OPr3)—; R7, R9 and R10 are the same or different and represent hydrogen or an amino acid side chain moiety from either a natural or an unnatural amino acid; Pr1 and Pr2 are the same or different and represent hydrogen or a thiol protecting group; Pr3 is hydrogen or an alcohol protecting group; R1, R2, R5 and R6 are the same or different and represent hydrogen or an amino acid side chain moiety from either a natural or an unnatural amino acid, or R1 and R2 and/or R5 and R6, taken together with the carbon atom to which they are attached, form a spirocyclic moiety, with the proviso that: each of R1 and R2 is not hydrogen, or each of R5 and R6 is not hydrogen.
- -
-
Page/Page column 30
(2011/05/16)
-
- Total synthesis of spiruchostatin B aided by an automated synthesizer
-
The total synthesis of a natural product HDAC inhibitor, spiruchostatin B, was successfully achieved. A 5-step synthesis that included an asymmetric aldol reaction was carried out in an automated synthesizer to provide an (E)-(S)-3-hydroxy-7-thio-4-heptenoic acid segment that is the crucial structure of cysteine-containing, depsipeptidic natural products such as spiruchostatins, FK228, FR901375, and largazole for their inhibitory activity against HDACs.
- Fuse, Shinichiro,Okada, Kumiko,Iijima, Yusuke,Munakata, Asami,MacHida, Kazuhiro,Takahashi, Takashi,Takagi, Motoki,Shin-Ya, Kazuo,Doi, Takayuki
-
p. 3825 - 3833
(2011/06/21)
-
- Macrolactamization versus macrolactonization: Total synthesis of FK228, the depsipeptide histone deacetylase inhibitor
-
(Chemical Equation Presented) The cyclic depsipeptide FK228 is the only natural product histone deacetylase (HDAC) inhibitor that has advanced to clinical trials as an anticancer agent. While currently obtained by fermentation, total synthesis is an 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.
- Wen, Shijun,Packham, Graham,Ganesan
-
experimental part
p. 9353 - 9361
(2009/04/05)
-
- A total synthesis of spiruchostatin A
-
We achieved the total synthesis of the histone deacetylase inhibitor spiruchostatin A, as the prelude to the preparation of a combinatorial library of its analogues. Two key reactions were an asymmetric acetate aldol reaction using a Zr-enolate and macrol
- Doi, Takayuki,Iijima, Yusuke,Shin-Ya, Kazuo,Ganesan,Takahashi, Takashi
-
p. 1177 - 1180
(2007/10/03)
-