Total synthesis of alkyl citrate and resorcylate natural products
Author(s)
Calo, Frederick
Type
Thesis
Abstract
The total synthesis of citrafungin A (i),1 the determination of the absolute
stereochemistry2 of CJ-13,981 (ii) and CJ-13,982 (iii) and the formal total synthesis of
(–)-trachyspic acid, by making lactone iv,3 were achieved from a common intermediate (v).
[Diagram omitted]
Dioxolanone v was prepared on a multigram scale starting from commercially available
4-benzyloxy-butyric acid using, as key steps, an enantioselective syn-aldol reaction of a
chiral oxazolidinone and a diastereoselective Seebach alkylation of a 1,3-dioxolan-2-one derivative.
[Diagram omitted]
From dioxolanone v, citrafungin A (i) was synthesised in 13 steps, CJ-13,981 (ii) and CJ-
13,982 (iii) in 9 steps and the intermediate lactone (iv) for the formal synthesis of
(–)-trachyspic acid in 5 steps.
Based on our recent advances on resorcylates metabolites,4 we carried out the total
synthesis of aigialomycin D (vi),5 a potent 14-membered resorcylic macrolide, without the
need for phenol protection, using the C-acylation of a keto-dioxinone dianion (or monoanion),
a cascade sequence consisting of ketene generation, alcohol (vii) trapping and
aromatization, and ring closing metathesis.
[Diagram omitted]
References:
(1) Calo, F.; Richardson, J.; Barrett, A. G. M. J. Org. Chem. 2008, 73, 9292.
(2) Calo, F.; Bondke. A.; Richardson, J.; White, A. J. P.; Barrett, A. G. M. Tetrahedron Lett.
2009, 50, 3388.
(3) Calo, F.; Richardson, J.; White, A. J. P.; Barrett, A. G. M. Tetrahedron Lett. 2009, 50, 1566.
(4) Navarro, I.; Basset, J.-F.; Hebbe, S.; Major, S.; Barrett, A. G. M. J. Am. Chem. Soc. 2008,
130, 10293.
(5) Calo, F.; Richardson, J.; Barrett, A. G. M. Org. Lett. 2009, 11, 4910-
stereochemistry2 of CJ-13,981 (ii) and CJ-13,982 (iii) and the formal total synthesis of
(–)-trachyspic acid, by making lactone iv,3 were achieved from a common intermediate (v).
[Diagram omitted]
Dioxolanone v was prepared on a multigram scale starting from commercially available
4-benzyloxy-butyric acid using, as key steps, an enantioselective syn-aldol reaction of a
chiral oxazolidinone and a diastereoselective Seebach alkylation of a 1,3-dioxolan-2-one derivative.
[Diagram omitted]
From dioxolanone v, citrafungin A (i) was synthesised in 13 steps, CJ-13,981 (ii) and CJ-
13,982 (iii) in 9 steps and the intermediate lactone (iv) for the formal synthesis of
(–)-trachyspic acid in 5 steps.
Based on our recent advances on resorcylates metabolites,4 we carried out the total
synthesis of aigialomycin D (vi),5 a potent 14-membered resorcylic macrolide, without the
need for phenol protection, using the C-acylation of a keto-dioxinone dianion (or monoanion),
a cascade sequence consisting of ketene generation, alcohol (vii) trapping and
aromatization, and ring closing metathesis.
[Diagram omitted]
References:
(1) Calo, F.; Richardson, J.; Barrett, A. G. M. J. Org. Chem. 2008, 73, 9292.
(2) Calo, F.; Bondke. A.; Richardson, J.; White, A. J. P.; Barrett, A. G. M. Tetrahedron Lett.
2009, 50, 3388.
(3) Calo, F.; Richardson, J.; White, A. J. P.; Barrett, A. G. M. Tetrahedron Lett. 2009, 50, 1566.
(4) Navarro, I.; Basset, J.-F.; Hebbe, S.; Major, S.; Barrett, A. G. M. J. Am. Chem. Soc. 2008,
130, 10293.
(5) Calo, F.; Richardson, J.; Barrett, A. G. M. Org. Lett. 2009, 11, 4910-
Date Issued
2009-12
Date Awarded
2010-05
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Barrett, Anthony
Creator
Calo, Frederick
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)