Biosynthesis of Strained Piperazine Alkaloids: Uncovering the Concise Pathway of Herquline A.
Nature synthesizes many strained natural products that have diverse biological activities. Uncovering these biosynthetic pathways may lead to biomimetic strategies for organic synthesis of such compounds. In this work, we elucidated the concise biosynthetic pathway of herquline A, a highly strained and reduced fungal piperazine alkaloid. The pathway builds on a nonribosomal peptide synthetase derived dityrosine piperazine intermediate. Following enzymatic reduction of the P450-cross-linked dicyclohexadienone, N-methylation of the piperazine serves as a trigger that leads to a cascade of stereoselective and nonenzymatic transformations. Computational analysis of key steps in the pathway rationalizes the observed reactivities.
School of Pharmaceutical Sciences, Central South University , Changsha, Hunan 410013, People's Republic of China.
Xia
X
Yu
Fang
F
Liu
Yi
Y
Zou
Man-Cheng
MC
Tang
Leibniz
L
Hang
K N
KN
Houk
Yi
Y
Tang
J Org Chem. 1996 Jan 26;61(2):771-774
11667003
J Am Chem Soc. 2006 Mar 29;128(12):3908-9
16551088
J Biol Chem. 2008 Nov 28;283(48):33406-16
18818197
J Org Chem. 2009 Feb 20;74(4):1581-6
19170539
Proc Natl Acad Sci U S A. 2009 May 5;106(18):7426-31
19416919
J Am Chem Soc. 2009 Jul 8;131(26):9172-3
19530671
Nat Chem Biol. 2010 Nov;6(11):797-9
20852636
Nat Chem. 2011 May;3(5):388-92
21505498
J Am Chem Soc. 2011 Nov 16;133(45):18010-3
21999343
Org Lett. 2012 May 4;14(9):2402-5
22519727
Nat Prod Rep. 2012 Aug;29(8):899-934
22729238
Angew Chem Int Ed Engl. 2013 Jan 28;52(5):1590-4
23281040
J Antibiot (Tokyo). 2014 Jan;67(1):31-41
24220108
Proteins. 2014 Jun;82(6):1004-21
24356896
J Am Chem Soc. 2016 Mar 30;138(12):4249-59
26978228
ACS Catal. 2016 Jul 1;6(7):4506-4511
28503354
J Antibiot (Tokyo). 1979 Aug;32(8):786-90
500499
J Antibiot (Tokyo). 1982 Sep;35(9):1130-6
7142019
J Antibiot (Tokyo). 1996 Jan;49(1):50-3
8609085