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Volumn 65, Issue 39, 2009, Pages 8283-8296

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

Author keywords

Isopilocarpine; Jaborandi alkaloids; Pilocarpine; Pilosinine

Indexed keywords

ALKALOID DERIVATIVE; ISOPILOCARPINE; LACTONE DERIVATIVE; PILOCARPINE;

EID: 69049102011     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tet.2009.07.010     Document Type: Article
Times cited : (26)

References (85)
  • 12
    • 0003796326 scopus 로고
    • The absolute (3S,4R)-configuration of (+)-pilocarpine 1 was established in 1966, see:
    • The absolute (3S,4R)-configuration of (+)-pilocarpine 1 was established in 1966, see:. Hill R.K., and Barcza S. Tetrahedron 22 (1966) 2889
    • (1966) Tetrahedron , vol.22 , pp. 2889
    • Hill, R.K.1    Barcza, S.2
  • 13
    • 77957059183 scopus 로고
    • Manske R.H.F., and Holmes H.L. (Eds), Academic, New York, NY
    • Battersby A.R., and Openshaw H.T. In: Manske R.H.F., and Holmes H.L. (Eds). The Alkaloids Vol. 3 (1953), Academic, New York, NY 201
    • (1953) The Alkaloids , vol.3 , pp. 201
    • Battersby, A.R.1    Openshaw, H.T.2
  • 14
    • 0000516905 scopus 로고
    • Brossi A. (Ed), Academic, New York, NY
    • Maat L., and Beyerman H.C. In: Brossi A. (Ed). The Alkaloids Vol. 22 (1983), Academic, New York, NY 281
    • (1983) The Alkaloids , vol.22 , pp. 281
    • Maat, L.1    Beyerman, H.C.2
  • 20
    • 0003680152 scopus 로고
    • Gilman A.G., Goodman L.S., and Gilman A. (Eds), Macmillan, New York, NY
    • Talyor P. In: Gilman A.G., Goodman L.S., and Gilman A. (Eds). The Pharmacological Basis of Therapeutics. 6th ed. (1980), Macmillan, New York, NY 96
    • (1980) The Pharmacological Basis of Therapeutics. 6th ed. , pp. 96
    • Talyor, P.1
  • 38
    • 69049095600 scopus 로고    scopus 로고
    • For additional references related to the synthesis of isopilocarpine 2, see
    • For additional references related to the synthesis of isopilocarpine 2, see:
  • 43
    • 69049115731 scopus 로고    scopus 로고
    • For additional references related to the syntheses of various analogues, see
    • For additional references related to the syntheses of various analogues, see:
  • 51
    • 69049121742 scopus 로고    scopus 로고
    • 2) are generally required for unactivated acetylenes. See:
    • 2) are generally required for unactivated acetylenes. See:
  • 55
    • 69049109333 scopus 로고    scopus 로고
    • note
    • Treatment of 9 under these conditions resulted in a change of colour of the solution from deep red to yellow, followed by the formation of a light brown precipitate.
  • 56
    • 69049091449 scopus 로고    scopus 로고
    • note
    • The formation of (E)-α-ethylidene lactone 5 presumably arises from the isomerisation of the initially formed α-vinyl lactone 8, under the influence of the basic imidazole ring.
  • 57
    • 69049114653 scopus 로고    scopus 로고
    • note
    • Since hydrogenation of exclusively (E)-5 gave a 72:28 mixture of pilocarpine 1 and isopilocarpine 2 in quantitative yield, and hydrogenation of an 88:12 mixture of (E)- and (Z)-α-ethylidene lactones 5 (obtained from our first generation racemic synthesis) produced a 70:30 mixture of pilocarpine 1 and isopilocarpine 2 in quantitative yield; this indicates that the double bond geometry within 5 does not have a major impact on the product distributions obtained.
  • 58
    • 69049108052 scopus 로고    scopus 로고
    • note
    • An authentic sample of (+)-pilocarpine 1 was kindly supplied by Macfarlan Smith Ltd., Edinburgh; base-catalysed epimerisation of this sample also provided a diastereoisomerically pure sample of (+)-isopilocarpine 2.
  • 59
    • 69049106013 scopus 로고    scopus 로고
    • For reviews, see
    • For reviews, see:
  • 63
    • 69049112405 scopus 로고    scopus 로고
    • For a comprehensive review of the use of lipases as biocatalysts in organic solvents, see
    • For a comprehensive review of the use of lipases as biocatalysts in organic solvents, see:
  • 67
    • 69049093350 scopus 로고    scopus 로고
    • note
    • 1H NMR spectroscopy with chiral shift reagents were unsuccessful, however conversion of 25 to its Mosher's ester derivative enabled ee determination, see Ref. 9 within.
  • 70
    • 69049090383 scopus 로고    scopus 로고
    • note
    • 3, and comparison with an authentic racemic sample.
  • 74
    • 69049108242 scopus 로고    scopus 로고
    • note
    • 3N complete racemisation of monoacetate 29 was observed after only 48 h.
  • 75
    • 69049110459 scopus 로고    scopus 로고
    • note
    • 1H NMR spectrum of the crude reaction mixture and pure product.
  • 76
    • 69049118705 scopus 로고    scopus 로고
    • note
    • 2, CO (1 atm), 20 °C, 17 h.
  • 82
    • 69049118704 scopus 로고    scopus 로고
    • note
    • 2 are added, see Ref. 26 within.
  • 83
    • 69049119784 scopus 로고    scopus 로고
    • note
    • 2 at 50 atm pressure in MeOH, giving a 72:28 mixture of 1:2, respectively. Interestingly Pearlman's catalyst showed a small preference for formation of isopilocarpine 2 (56:44 mixture).


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.