- HETEROARYLCARBOXYLIC ACID ESTER DERIVATIVE
-
The present invention provides a hyperglycemic inhibitor having a serine protease inhibitory action, which is a novel prophylactic or therapeutic drug for diabetes. A compound represented by the following formula (I), wherein each symbol is as defined in the description, or a pharmaceutically acceptable salt thereof
- -
-
Page/Page column 25
(2012/11/06)
-
- Process for preparation of oxyglutaric acid ester derivatives
-
A process for preparing an oxyglutaric acid ester derivative of the formula: STR1 in which each of R1 and R2 is C1-5 alkoxy, C1-7 aralkyloxy, C7-9 halogenated aralkyloxy or phenyl, R4 is a hydroxyl-protecting group, and R5 is C1-10 alkyl which may have a substituent, comprises the steps of reacting a methyl phosphonate derivative or methyl phosphine oxide derivative with an oxyglutaric acid mono-ester to give a reaction product which comprises an oxyglutaric acid derivative having a phosphorus-containing group and a pentenedioic acid mono-ester (by-product), removing the pendenedioic acid mono-ester from the reaction product to isolate the oxyglutaric acid derivative, and converting the isolated oxyglutaric acid derivative into the oxyglutaric acid ester derivative. A process for obtaining an optically active oxyglutaric acid ester derivative is also disclosed.
- -
-
-
- Cyclopropanesulfonyl Chloride: Its Mechanism of Hydrolysis and Reactions with Tertiary Amines in Organic Media
-
Cyclopropanesulfonyl chloride (1) has been synthesized and its reactions examined to see if the three-membered ring leads to unusual reactions in either 1 or the corresponding sulfene, cyclopropanethione S,S-dioxide (2). pH-rate profiles, primary kinetic isotope effects (KIE's), and pH-product ratio experiments are in full agreement with mechanisms of hydrolysis of 1 like those of a simple alkanesulfonyl chlorides (J.Am.Chem.Soc.1992,114,1743-1749), specifically, (a) below pH 7.2 by SN2-S reaction with water and (b) above pH 7.3, elimination by hydroxide to form the sulfene (2) which is trapped by (i) water below pH 12.0 and (ii) hydroxide above pH 12.0.The products of the reaction of cyclopropanesulfonyl-1-d chloride (9) with triethylamine and 2-propanol in dichloromethane indicate that most of the reaction goes via 2; the analogous reaction with trimethylamine apparently proceeds by a direct formation of the sulfonylammonium chloride (14) which then yields the α-deuterated N,N-dimethyl sulfonamide (12, R=Me).The evident sulfene formation processes in the reaction of triethylamine with ethenesulfonyl, 2-propanesulfonyl, and cyclopropanesulfonyl chlorides show very low primary KIE's (1.5), pointing to highly product-like transition states.Reaction of 1 with an enamine (1-pyrrolidino-2-methylpropene, 20) in the presence of a base in either water or dichloromethane gave cyclopropanesulfonpyrrolidide (23) and an aldehyde adduct (24), but no four-membered cycloadduct (21).
- King, James F.,Lam, Joe Y. L.,Ferrazzi, Gabriele
-
p. 1128 - 1135
(2007/10/02)
-
