[EN] TUBULYSIN ANALOGS AND METHODS<br/>[FR] ANALOGUES DE TUBULYSINE ET PROCÉDÉS ASSOCIÉS
申请人:ENDOCYTE INC
公开号:WO2017031209A1
公开(公告)日:2017-02-23
The present disclosure relates to tubulysin derivatives and methods for making the same. The disclosure also relates to the use of such tubulysin derivatives in the preparation of drug conjugates of tubulysins.
into the unsaturated ester 30, acylation of the sulfone 47 using this ester, reductive desulfurisation, methylenation using a Wittig reaction and deprotection. Following model studies, the aldehyde 62, prepared by oxidation of the alcohol 51, was converted into a mixture of the epimeric alcohols 63 and these were converted into the di(methylene)tridecadienoic acid 65 using a phosphine catalysed Ireland–Claisen
The SN2 reactions having a symmetrical transition state were studied in a dipolar aprotic solvent. A good Hammett correlation was found for the chlorine isotopic exchangereactions in acetonitrile between tetraethylammonium chloride and three types of substituted methyl chlorides, 2-arylethyl chlorides, chloromethyl aryl ethers, and chloromethyl aryl sulfides. The reaction constant was positive for
Process for the preparation of substituted pyrrolidine neuraminidase inhibitors
申请人:——
公开号:US20030055297A1
公开(公告)日:2003-03-20
A process for the preparation of neuraminidase inhibitors having structural formula (28)
1
or therapeutically acceptable salts thereof, in which R
1
is alkyl, cycloalkyl, cycloalkylalkyl, or arylalkyl; R
2
is alkyl, cycloalkyl, cycloalkylalkyl, or arylalkyl; R
4
is alkyl, cycloalkyalkyl, or aryl-(C
2
-C
4
-alkyl); R
10
is methyl, ethyl, iso-propyl, or vinyl; and
R
12
is hydrogen or alkyl and intermediates useful for the process are disclosed.
作者:Derrick L. J. Clive、Yunxin Bo、Yong Tao、Sylvain Daigneault、Yong-Jin Wu、Gérard Meignan
DOI:10.1021/ja980292s
日期:1998.10.1
(E)-3-nitropropenoate to afford ketone 27. This was converted by two routes into (±)-calicheamicinone (1). In the first, modification of the nitro, ester, and allyl substituents gave ketone 38, which reacted stereoselectively with cerium trimethylsilylacetylide to place the acetylene unit syn to the nitrogen function (38 → 39). Further elaboration took the route as far as aldehyde 42. A slightly different series of