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. 2020 May 20;25(10):2377.
doi: 10.3390/molecules25102377.

A Convenient Synthesis of (16 S,20 S)-3β-hydroxy-5α-pregnane-20,16-carbolactam and its N-alkyl Derivatives

Agnieszka Wojtkielewicz  1 , Damian Pawelski  1 , Przemysław Bazydło  1 , Aneta Baj  1 , Stanisław Witkowski  1 , Jacek W Morzycki  1
Affiliations

A Convenient Synthesis of (16 S,20 S)-3β-hydroxy-5α-pregnane-20,16-carbolactam and its N-alkyl Derivatives

Agnieszka Wojtkielewicz et al. Molecules. .

Abstract

A concise synthesis of (16S,20S)-3β-hydroxy-5α-pregnane-20,16-carbolactam from tigogenin via the corresponding lactone is described. The most efficient synthetic route consisted of the lactone ring-opening with aminoalane reagent followed by PDC or Dess-Martin oxidation. The oxo-amide obtained was subjected to cyclization with Et3SiH/TFA or Et3SiH/Bi(TfO)3. Alternately, the lactone was converted first to the oxo-acid, which was then subjected to the microwave-assisted reductive amination. N-Alkyl derivatives were also obtained in a similar way.

Keywords: lactams; reductive amination; spirostane degradation; steroids.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Vespertilin, the target lactam, tigogenin, and steroidal alkaloids.
Scheme 1
Scheme 1
Synthesis of bisnorcholanic lactam derivatives via oxo-amide intermediates.
Figure 2
Figure 2
NOE and ROESY correlations diagram for compounds 4a.
Scheme 2
Scheme 2
Synthesis of bisnorcholanic lactam derivatives via an oxo-acid intermediate.
See this image and copyright information in PMC

References

    1. Jastrzebska I. Synthesis and application of steroidal 22,16β-carbolactones: A review. J. Steroid Biochem. Mol. Biol. 2020;199:105592. doi: 10.1016/j.jsbmb.2020.105592. - DOI - PubMed
    1. Gonzales A.G., Garcia F.C., Freire R., López E.S. Nuevas fuentes naturales de sapogeninas esteroidales. IX. Solanum Vespertilio Ait. An. Química. 1971;67:433–439.
    1. Zheng Q.-A., Zhang Y.-J., Li H.-Z., Yang C.-R. Steroidal saponins from fresh stem of Dracaena cochinchinensis. Steroids. 2004;69:111–119. doi: 10.1016/j.steroids.2003.11.004. - DOI - PubMed
    1. Ahmad V.U., Khaliq-Uz-Zaman S.M., Shameel S., Perveen S., Ali Z. Steroidal saponins from Asparagus dumosus. Phytochemistry. 1999;50:481–484. doi: 10.1016/S0031-9422(98)00566-4. - DOI - PubMed
    1. Yin J., Han N., Liu Z., Song S., Kadota S. The in vitro antiosteoporotic activity of some glycosides in Dioscorea spongiosa. Biol. Pharm. Bull. 2010;33:316–320. doi: 10.1248/bpb.33.316. - DOI - PubMed

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