35594-23-1Relevant academic research and scientific papers
Syntheses of the racemic jaborandi alkaloids pilocarpine, isopilocarpine and pilosinine
Davies, Stephen G.,Roberts, Paul M.,Stephenson, Peter T.,Thomson, James E.
, p. 3509 - 3512 (2009)
The synthesis of racemic pilocarpine has been achieved in high overall yield. Two alternative approaches for the formation of the γ-butyrolactone ring are described: the first involves a palladium-catalysed carbonylation reaction of a homopropargylic alco
A practical and scaleable total synthesis of the jaborandi alkaloid (+)-pilocarpine
Davies, Stephen G.,Roberts, Paul M.,Stephenson, Peter T.,Storr, Helen R.,Thomson, James E.
experimental part, p. 8283 - 8296 (2009/12/28)
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.
Convergent diastereoselective synthesis of isopilocarpine by one-pot Michael-addition-alkylation reaction
Braun, Manfred,Buehne, Corinna,Cougali, Dimitrula,Schaper, Klaus,Frank, Walter
, p. 2905 - 2909 (2007/10/03)
The metalated dithiane 7b available from imidazole aldehyde 6 is reacted with furanone 4 and ethyl iodide to give the lactone 8, which forms diastereoselectively. Its configuration is determined to be trans by means of a crystal structure analysis. The desulfurization of 8 leads to the alkaloid isopilocarpine 2 in three steps and 25% overall yield. The relative energies of the diastereomeric alkaloids 1 and 2 have been calculated.
