Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Synthetic Studies Concerning the Crinine Alkaloid Haemultine

Nadia (Yuqian) Gao A , Xinghua Ma A , Laurent Petit A , Brett D. Schwartz A , Martin G. Banwell A B , Anthony C. Willis A , Ian A. Cade A and A. David Rae A

A Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT 0200, Australia.

B Corresponding author. Email: mgb@rsc.anu.edu.au

Australian Journal of Chemistry 66(1) 30-39 http://dx.doi.org/10.1071/CH12473
Submitted: 15 October 2012  Accepted: 9 November 2012   Published: 14 January 2013

Abstract

The racemic form, (±)-1, of the structure originally assigned to the crinine alkaloid haemultine has been prepared for the first time. A key step involved the conversion of compound (±)-4 into the isomeric cis-C3a-arylhexahydroindole (±)-3 using a Pd0-catalysed intramolecular Alder-ene reaction. The amino-alcohol (±)-2 derived from the latter compound reacted with paraformaldehyde in the presence of trifluoroacetic acid to give, via a Pictet–Spengler reaction, the target (±)-1. The diastereoisomeric Mosher esters 15 and 16 obtained by coupling the racemate (±)-1 with the R-form, 14, of the Mosher acid could be separated chromatographically and then reductively cleaved to give the enantiomerically pure compounds (+)-1 and (–)-1, respectively. The physical and spectroscopic data derived from the former enantiomer are consistent with the proposition that the title natural product is, in fact, a mixture of (+)-1 and its Δ2,3-double bond isomer.

Graphical Abstract Image


References

[1]  S. C. Chhabra, B. L. A. Mahunnah, E. N. Mshiu, J. Ethnopharmacol. 1987, 21, 253.
         | CrossRef | 1:STN:280:DyaL1c7ls1aqtQ%3D%3D&md5=427e772a8c11ed2065b4a0e243c2906dCAS | open url image1

[2]  H.-G. Boit, W. Döpke, Chem. Ber. 1958, 91, 1965.
         | CrossRef | 1:CAS:528:DyaG1MXhsleqsA%3D%3D&md5=ab382490f489c329b2c4d8d9d6b3f501CAS | open url image1

[3]  M. M. Iwu, Handbook of African Medicinal Plants, 1993 (CRC Press: Boca Raton, FL) and references therein.

[4]  H. M. Fales, W. C. Wildman, J. Org. Chem. 1961, 26, 1617.
         | CrossRef | 1:CAS:528:DyaF3MXhtlWnsro%3D&md5=0cea50b1b5aec509f4b73db81b630a52CAS | open url image1

[5]  H. M. Fales, W. C. Wildman, J. Am. Chem. Soc. 1958, 80, 4395.
         | CrossRef | 1:CAS:528:DyaG1MXitlCmtw%3D%3D&md5=29e15326ae2330f59c6d1b8d075b66d2CAS | open url image1

[6]  O. M. Abdallah, A. A. Ali, H. Itokawa, Phytochemistry 1989, 28, 3248.
         | CrossRef | 1:CAS:528:DyaK3cXpsFCqtA%3D%3D&md5=293a62754f2ebbbd60cfad4a04ed7e58CAS | open url image1

[7]  C.-K. Chen, F.-H. Lin, L.-H. Tseng, C.-L. Jiang, S.-S. Lee, J. Nat. Prod. 2011, 74, 411.Both enantiomeric forms of the crinine alkaloid framework are encountered in nature. See, for example:
         | CrossRef | 1:CAS:528:DC%2BC3MXhvVWisrY%3D&md5=9ea1e3979015d77fe10d7912ae03a926CAS | open url image1

[8]  (a) L. E. Overman, S. Sugai, Helv. Chim. Acta 1985, 68, 745.For representative examples of crinine alkaloid syntheses reported over the preceding three decades or so see:
         | CrossRef | 1:CAS:528:DyaL2MXlsVahsbo%3D&md5=78a20bda8048198fb404038e95d9d621CAS | open url image1
      (b) W. H. Pearson, F. E. Lovering, Tetrahedron Lett. 1994, 35, 9173.
         | CrossRef | open url image1
      (c) C. Bru, C. Guillou, Tetrahedron 2006, 62, 9043.
         | CrossRef | open url image1
      (d) M. Bohno, K. Sugie, H. Imase, Y. B. Yusof, T. Oishi, N. Chida, Tetrahedron 2007, 63, 6977.
         | CrossRef | open url image1
      (e) N. T. Tam, J. Chang, E.-J. Jung, C.-G. Cho, J. Org. Chem. 2008, 73, 6258.
         | CrossRef | open url image1
      (f) J.-D. Liu, S.-H. Wang, F.-M. Zhang, Y.-Q. Tu, Y.-Q. Zhang, Synlett 2009, 3040.and references therein open url image1

[9]  (a) M. G. Banwell, J. E. Harvey, K. A. Jolliffe, J. Chem. Soc., Perkin Trans. 1 2001, 2002.Various syntheses of crinine alkaloids have been reported by our group see:
         | CrossRef | 1:CAS:528:DC%2BD3MXmsF2kuro%3D&md5=fd48a8c20405aeed98bfd32a08bde7d5CAS | open url image1
      (b) A. D. Findlay, M. G. Banwell, Org. Lett. 2009, 11, 3160.
         | CrossRef | open url image1
      (c) L. Petit, M. G. Banwell, A. C. Willis, Org. Lett. 2011, 13, 5800.
         | CrossRef | open url image1

[10]  A. L. Lehmann, A. C. Willis, M. G. Banwell, Aust. J. Chem. 2010, 63, 1665.
         | CrossRef | 1:CAS:528:DC%2BC3cXhsFaqsbvL&md5=94a8fcdf4ec549d910af97e33a0ef7b7CAS | open url image1

[11]  M. G. Banwell, N. (Y.) Gao, B. D. Schwartz, L. V. White, Top. Curr. Chem. 2012, 309, 163.For a summary of the various alkaloid syntheses that have been undertaken within our group see:
         | CrossRef | 1:CAS:528:DC%2BC38XntlOksrg%3D&md5=c1cbc84af13956aab83cdc09443ed02cCAS | open url image1

[12]  (a) M. G. Banwell, D. A. S. Beck, P. C. Stanislawski, M. O. Sydnes, R. M. Taylor, Curr. Org. Chem. 2005, 9, 1589.For discussions on the application of gem-dihalocyclopropanes in natural product synthesis see:
         | CrossRef | 1:CAS:528:DC%2BD2MXhtVakt7rF&md5=4a36365784ca201b5377a786a1baa44cCAS | open url image1
      (b) M. G. Banwell, A. L. Lehmann, R. S. Menon, A. C. Willis, Pure Appl. Chem. 2011, 83, 411.
         | CrossRef | open url image1

[13]  J. Sonnenberg, S. Winstein, J. Org. Chem. 1962, 27, 748.
         | CrossRef | 1:CAS:528:DyaF38XktFKlt7g%3D&md5=424d2d0b28079eab957d147f5283e86dCAS | open url image1

[14]  M. G. Banwell, C. J. Cowden, Aust. J. Chem. 1994, 47, 2235.
         | CrossRef | 1:CAS:528:DyaK2MXisl2mt78%3D&md5=15fd55e227902189f3de7e324dd3a50eCAS | open url image1

[15]  N. Miyaura, T. Yanagi, A. Suzuki, Synth. Commun. 1981, 11, 513.
         | CrossRef | 1:CAS:528:DyaL3MXmtVems7w%3D&md5=f46b8f83503a40d6d46368e6ca16521bCAS | open url image1

[16]  B. M. Trost, C. Pedregal, J. Am. Chem. Soc. 1992, 114, 7292.
         | CrossRef | 1:CAS:528:DyaK38XltFWnsLY%3D&md5=6ed2d50cb11b296b8bc929b948c9ddbaCAS | open url image1

[17]  A. R. Carroll, W. C. Taylor, Aust. J. Chem. 1990, 43, 1439.and references cited therein
         | CrossRef | 1:CAS:528:DyaK3MXktFKlsA%3D%3D&md5=1de006d939c45679fa292a0be9c15300CAS | open url image1

[18]  T. Fukuyama, C.-K. Jow, M. Cheung, Tetrahedron Lett. 1995, 36, 6373.
         | CrossRef | 1:CAS:528:DyaK2MXnvFCmu7k%3D&md5=83e3a8b48577f4451405f204a727fbe9CAS | open url image1

[19]  T. R. Hoye, C. S. Jeffrey, F. Shao, Nat. Protoc. 2007, 2, 2451.
         | CrossRef | 1:CAS:528:DC%2BD2sXhtFOksL3E&md5=cd2e89c6c9c2c40ac215fbce38aec9abCAS | open url image1

[20]  W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43, 2923.
         | CrossRef | 1:CAS:528:DyaE1cXksF2hu7s%3D&md5=01710b05420a1d62d2d09684f9f52747CAS | open url image1

[21]  A. B. Pangborn, M. A. Giardello, R. H. Grubbs, R. K. Rosen, F. J. Timmers, Organometallics 1996, 15, 1518.
         | CrossRef | 1:CAS:528:DyaK28XhtVerur0%3D&md5=32bd3edcd3b0c9cb1240001cb646da4fCAS | open url image1

[22]  DENZO–SMN. Z. Otwinowski, W. Minor, Processing of X-ray diffraction data collected in oscillation mode, in Methods in Enzymology, Volume 276: Macromolecular Crystallography, Part A (Eds C. W. Carter, Jr, R. M. Sweet) 1997, pp. 307–326 (Academic Press: New York, NY).

[23]  SIR92. A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. C. Burla, G. Polidori, M. Camalli, J. Appl. Cryst. 1994, 27, 435. open url image1

[24]  P. W. Betteridge, J. R. Carruthers, R. I. Cooper, K. Prout, D. J. Watkin, J. Appl. Cryst. 2003, 36, 1487.
         | CrossRef | 1:CAS:528:DC%2BD3sXptFekt78%3D&md5=27ab58411389a62e3ab495bba39187feCAS | open url image1

[25]  A. D. Rae, RAELS06, 2006 (The Australian National University: Canberra).



Supplementary MaterialSupplementary Material (2.3 MB) Export Citation