A practical and scaleable total synthesis of the jaborandi alkaloid (+)-pilocarpine

Journal article

The total synthesis of (+)-pilocarpine (as its nitrate salt) has been achieved in nine steps and 30% overall yield starting from racemic 2-(2′,2′-dimethoxyethyl)propane-1,3-diol, which was desymmetrised via an enzymatic protocol. A high yielding synthesis of a key α-ethylidene lactone precursor has been developed, which involves the palladium-catalysed decarboxylation/carbonylation of a 1,3-dioxan-2-one for formation of the γ-butyrolactone ring. Subsequent hydrogenation of the α-ethylidene lactone introduces the C(3)-stereochemistry to give a 72:28 mixture of (+)-pilocarpine and (+)-isopilocarpine, which are readily separable via recrystallisation of the (+)-pilocarpine nitrate salt. © 2009 Elsevier Ltd. All rights reserved.

Authors: Davies, S; Roberts, P; Stephenson, P; Storr, H; Thomson, J

• Publication status: Published
• Journal: TETRAHEDRON
• Volume: 65
• Issue: 39
• Pages: 8283-8296
• Publication date: 2009-09-26
• DOI: 10.1016/j.tet.2009.07.010
• ISSN: 0040-4020
• Language: English
• Keywords: Pilocarpine; Jaborandi alkalids; Pilosinine; Isopilocarpine