Hydroxylation of the double bond in 1-benzyl-3-methyl-Δ3-piperidine by mycelium fungi

Abstract

Chiral polyhydroxypiperidine derivatives have recently attracted attention due to the anticancer and antiviral properties displayed by some of these compounds [1][2][3]. However, the enantioseleetive synthesis of such compounds is difficult and laborious [4]. On the other hand, the microbiological oxidation of organic compounds, in particular, nitrogen heterocycles, proceeds, as a rule, with regio-and enantioselectivity [5][6][7][8].We have studied the microbiological oxidation of 1-benzyl-3-methyl-A3-piperidine (I) by mycelium fungi.Of the five strains of Aspergillus niger, two strain.~ of Beauveria bassiana, Rizopus oryzae VKPM 1::-431, Penicillium simplicissimum and Cunninghamella verticillata VKPM F-430, the latter fungus proved the most active [9]. T.h.e transformation was carried out in a growing cell culture of these fungus strains at pH 5.0 according to our previous procedure [10]. The concentration of substrate for the transformation was 100 rag/liter. The transformation products were extracted thrice with chloroform from the culture liquid at pH 10.0. The chloroform extracts were evaporated to dryness and the residue was dissolved in a small amount of methanol and analyzed on an HP-5890 Series II GC/MS with HP 5972 mass-selective detector equipped with a 30 m • 0.2 mm quartz capillary column packed with HP-5MS as the stationary phase. Temperature programming was carried out at from 70 to 250~ at 30~

Enantioselective Trans Dihydroxylation of Nonactivated C−C Double Bonds of Aliphatic Heterocycles withSphingomonassp. HXN-200

“…Successful examples are the fungus-catalyzed trans dihydroxylations of several acyclic terpenes, − limonene, and α-terpinene . However, enantioselective trans dihydroxylation of a nonisoprene C−C double bond has been synthetically unsuccessful: several eukaryotic systems (plants, animal, and fungi) were known to metabolize aromatic compounds transforming the C−C double bond into the corresponding trans -dihydrodiol with low yield; bioconversion of 1-benzyl-3-methyl-1,2,5,6-tetrahydropyridine with Cunninghamella verticillata VKPM F-430 gave a mixture of 3,4- trans -diol and two monohydroxylated products . Moreover, trans dihydroxylation catalysts reported so far are limited to the eukaryotic systems.…”

Microorganisms in Chemistry of Terpenoids

“…Hydroxylated derivatives of artemisinins obtained by microbial techniques may be used to create hybrid molecules based on molecules of nitrogenous heterocycles (Dovgilevich et al, 1991;Khasaeva et al, 2014;Modyanova et al, 1999Modyanova et al, , 2010Parshikov et al, 1992Parshikov et al, , 1997Parshikov et al, , 1999aParshikov et al, ,b,c, 2000aParshikov et al, ,b,c,d, 2001aParshikov et al, ,b,c,d, 2002aParshikov et al, ,b,c,d, 2010bSutherland et al, 2001;Terentyev et al, 1989Terentyev et al, , 1997Terentyev et al, , 2010Williams et al, 2001Williams et al, , 2004Williamson et al, 2007).…”

Microbial Transformation of Nitrogen Containing Heterocycles

“…During the transformation of 1-benzyl-3-methyl-Δ 3piperidine (LIV) by growing mycelia of C. verticillata , three products were observed in a ratio of LV: LVI: LVII = 1:2:16 (Terent'ev et al 1997):…”