Novel convenient synthesis of biologically active esters of hydroxylamine.
Alkylation of ethyl N-hydroxyacetimidate with readily available methanesulfonates of functionally substituted alcohols and subsequent deprotection of aminooxy group is a novel and convenient method to prepare functionally substituted esters of hydroxylamine with high overall yield. This approach is a good alternative to well-known reaction of N-hydroxyphthalimide with alcohols under the Mitsunobu conditions. The properties of ethoxyethylidene protection of aminooxy group on the contrary to that of N-alkoxyphthalimide group allow to perform a wide spectra of the transformations in the radical of N-protected hydroxylamine derivatives. This is essential for synthetic strategies consisting in the introduction of N-protected aminooxy group at one of the first steps of synthesis and subsequent transformations of the radical.The inhibitory effect of one of the newly synthesized compound, 1-guanidinooxy-3-aminopropane (GAPA), was compared with that of well-known inhibitors of ornithine decarboxylase namely, alpha-difluoromethylornithine (DFMO) and 1-aminooxy-3-aminopropane (APA) on Leishmania donovani, a protozoan parasite that causes visceral leishmaniasis. GAPA, on the contrary with APA and DFMO, in micromolar concentrations, inhibited the growth of both amastigotes and promastigotes of sodium antimony gluconate-resistant forms of L. donovani.
Khomutov
Maxim A
MA
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. hommaximus@mail.ru
Mandal
Swati
S
Weisell
Janne
J
Saxena
Neiha
N
Simonian
Alina R
AR
Vepsalainen
Jouko
J
Madhubala
Rentala
R
Kochetkov
Sergey N
SN
D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D019811:Hydroxylamine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007893:Leishmania donovani / Q000187:drug effects / Q000254:growth & development; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000469:parasitology; D011437:Propylamines / Q000494:pharmacology
D000981:Antiprotozoal Agents; D004952:Esters; D011437:Propylamines; D019811:Hydroxylamine; C046252:1-aminooxy-3-aminopropane