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Volumn 49, Issue 50, 2010, Pages 9693-9698

Synthetic and theoretical investigations of myrmicarin biosynthesis

Author keywords

dienamines; iminium ion; Knorr pyrrole synthesis; myrmicarins; total synthesis

Indexed keywords

DIENAMINES; IMINIUM; KNORR PYRROLE SYNTHESIS; MYRMICARINS; TOTAL SYNTHESIS;

EID: 78650127882     PISSN: 14337851     EISSN: 15213773     Source Type: Journal    
DOI: 10.1002/anie.201005825     Document Type: Article
Times cited : (32)

References (44)
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    • For the subsequent use of one of these building blocks to prepare a member of a distinct natural product family, see
    • S. A. Snyder, S. P. Breazzano, A. G. Ross, Y. Lin, A. L. Zografos, J. Am. Chem. Soc. 2009, 131, 1753-1765. For the subsequent use of one of these building blocks to prepare a member of a distinct natural product family, see
    • (2009) J. Am. Chem. Soc. , vol.131 , pp. 1753-1765
    • Snyder, S.A.1    Breazzano, S.P.2    Ross, A.G.3    Lin, Y.4    Zografos, A.L.5
  • 22
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    • Angew. Chem. Int. Ed. 2010, 49, 5146-5150.
    • (2010) Angew. Chem. Int. Ed. , vol.49 , pp. 5146-5150
  • 23
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    • A related biosynthetic hypothesis has been advanced by Francke and Schröder, though it invokes cross-conjugated endocyclic dienamines that differ from 9: see Ref. [1b].
    • A related biosynthetic hypothesis has been advanced by Francke and Schröder, though it invokes cross-conjugated endocyclic dienamines that differ from 9: see Ref. [1b].
  • 27
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    • This literature report characterized the major product as the E-isomer; however, no justification was given for the stereochemical assignment. In our hands, this procedure almost exclusively leads to the Z-isomer, even on substrates included in the initial report. A similar Z-selectivity has been observed in other Lewis acid mediated linear crotylations and an open transition state has been proposed to account for this outcome
    • Y. Yamamoto, K. Maruyama, J. Org. Chem. 1983, 48, 1564-1565. This literature report characterized the major product as the E-isomer; however, no justification was given for the stereochemical assignment. In our hands, this procedure almost exclusively leads to the Z-isomer, even on substrates included in the initial report. A similar Z-selectivity has been observed in other Lewis acid mediated linear crotylations and an open transition state has been proposed to account for this outcome
    • (1983) J. Org. Chem. , vol.48 , pp. 1564-1565
    • Yamamoto, Y.1    Maruyama, K.2
  • 29
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    • 2O was required to prevent isomerization to the α,β-unsaturated ketone, a molecule which proved recalcitrant to cyclization.
    • 2O was required to prevent isomerization to the α,β-unsaturated ketone, a molecule which proved recalcitrant to cyclization.
    • (1998) Bioorg. Med. Chem. Lett. , vol.8 , pp. 357-360
    • Ripka, A.S.1    Bohacek, R.S.2    Rich, D.H.3
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    • Cold NaOH was critical to obtaining high yields in this reaction.
    • Cold NaOH was critical to obtaining high yields in this reaction.
  • 31
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    • Although we use the term "stable", these compounds cannot be purified on deactivated silica gel, neutral alumina, or basic alumina and must be used directly following extraction without further purification.
    • Although we use the term "stable", these compounds cannot be purified on deactivated silica gel, neutral alumina, or basic alumina and must be used directly following extraction without further purification.
  • 32
    • 78650100476 scopus 로고    scopus 로고
    • The natural product myrmicarin 237 (the fully saturated form of 9) also lacks configurational stability at the α-position. Calculations suggest that the level of pyramidalization about nitrogen in 18 - 21 is less than in either their monoenamine counterparts or myrmicarin 237, which may account for their observed configurational stability.
    • The natural product myrmicarin 237 (the fully saturated form of 9) also lacks configurational stability at the α-position. Calculations suggest that the level of pyramidalization about nitrogen in 18-21 is less than in either their monoenamine counterparts or myrmicarin 237, which may account for their observed configurational stability.
  • 33
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    • We found that dissolving 18 and 19 in either pH 7.4 or 8.6 aqueous buffers also led to the clean formation of myrmicarin 215A and B (1 and 2), suggesting that 1 - 3 are spontaneously formed upon oxidation of the n-butyl sidechain in myrmicarin 237-like structures. Although these experiments cannot rule out the possibility of other biosynthetic precursors, the above hypothesis is strengthened by the structural features found in the natural isolates myrmicarin 237 and 663 (6).
    • We found that dissolving 18 and 19 in either pH 7.4 or 8.6 aqueous buffers also led to the clean formation of myrmicarin 215A and B (1 and 2), suggesting that 1-3 are spontaneously formed upon oxidation of the n-butyl sidechain in myrmicarin 237-like structures. Although these experiments cannot rule out the possibility of other biosynthetic precursors, the above hypothesis is strengthened by the structural features found in the natural isolates myrmicarin 237 and 663 (6).
  • 34
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    • For a review on dienamines, see.
    • For a review on dienamines, see:, P. W. Hickmott, Tetrahedron 1984, 40, 2989-3051.
    • (1984) Tetrahedron , vol.40 , pp. 2989-3051
    • Hickmott, P.W.1
  • 35
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    • A number of experiments demonstrated that the desired ethyl epimer cyclizes to 26 faster than the undesired epimer. Performing the reaction in isopropyl alcohol allowed for a sufficiently low overall rate of cyclization to achieve a kinetic resolution leading to up to a 5:1 d.r., albeit in reduced yield (12 %).
    • A number of experiments demonstrated that the desired ethyl epimer cyclizes to 26 faster than the undesired epimer. Performing the reaction in isopropyl alcohol allowed for a sufficiently low overall rate of cyclization to achieve a kinetic resolution leading to up to a 5:1 d.r., albeit in reduced yield (12 %).
  • 36
    • 78650114366 scopus 로고    scopus 로고
    • The reduced d.r. observed in these reactions compared to myrmicarin 215 dimerizations may be a reflection of the conformational flexibility in the dienamine sidechain as well as the less sterically demanding environment of the electrophilic site, thereby allowing for some approach from the concave face of the electrophile to occur. The Supporting Information section contains a listing of various combinations and the resultant product ratios.
    • The reduced d.r. observed in these reactions compared to myrmicarin 215 dimerizations may be a reflection of the conformational flexibility in the dienamine sidechain as well as the less sterically demanding environment of the electrophilic site, thereby allowing for some approach from the concave face of the electrophile to occur. The Supporting Information section contains a listing of various combinations and the resultant product ratios.
  • 37
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    • -1
    • -1.
  • 41
    • 78650090309 scopus 로고    scopus 로고
    • Calculations were performed with Jaguar, version 7.6, Schrödinger, LLC, New York, NY, 2009. See the Supporting Information section for full details of the ab initio calculations. Cartesian coordinates and raw energies are also provided therein.
    • Calculations were performed with Jaguar, version 7.6, Schrödinger, LLC, New York, NY, 2009. See the Supporting Information section for full details of the ab initio calculations. Cartesian coordinates and raw energies are also provided therein.
  • 44
    • 78650102233 scopus 로고    scopus 로고
    • The proposed structure of myrmicarin 430B is shown below; it was found to convert spontaneously to myrmicarin 430A upon standing: F. Schröder, Ph.D. Thesis, University of Hamburg (Germany), 1996.
    • The proposed structure of myrmicarin 430B is shown below; it was found to convert spontaneously to myrmicarin 430A upon standing: F. Schröder, Ph.D. Thesis, University of Hamburg (Germany), 1996.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.