Synthesis of C-Nor-D-homo-steroidal Alkaloids and Their Derivatives

^§ Both authors contributed equally to this work.

Abstract

The C-nor-D-homo-steroidal alkaloid cyclopamine was discovered in the 1969 and in 2000 it was shown to act as an inhibitor of the hedgehog signaling (Hh) pathway, which is aberrantly activated in some tumors. Subsequently it was revealed that this natural occurring alkaloid has also antidiabetic and antiviral properties. In this review we present syntheses of selected C-nor-D-homo-steroidal alkaloids and their analogues and also discuss a general access to C-nor-D-homo-steroids. Some historical as well as biomedical aspects are also presented.

1 Introduction

2 Total Synthesis of Cyclopamine

2.1 Synthesis of exo-Cyclopamine and Further Cyclopamine Analogues

2.2 Synthesis of a Carbacyclopamine Analogue

3 D-Homocyclopamine: Saridegib (IPI-926)

4 Synthesis of Nakiterpiosin

5 Lewis Acid Mediated Nazarov Cyclization as a Versatile Method for C-Nor-D-homo-steroid Synthesis

6 Conclusion

Key words

alkaloids - steroid - antitumor agents - ring closure - spiro compounds - stereoselective synthesis

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