Procedure-Economical, Enantioselective Total Syntheses of Polycyclic Natural Products and Analogues Containing a 3a-Hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic Acid Residue

Dedicated to the memory of the late Professor Shao-Min Zhou for his contribution to electrochemistry.

Abstract

The 3a-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid (HPIC) residue and its aza-analogue are found in many bioactive natural products. In this account, short divergent total syntheses of several such natural products, diastereomers and analogues are described. It is demonstrated that by appropriate combination of different efficient tactics such as biomimetic/bio-inspired synthesis, chemo/regioselective reactions, umpolung of regioselectivity and/or reactivity, and tandem reactions, the enantioselective syntheses of polycyclic molecules such as (+)-asperlicin E and (–)-robustanoids A and B can be achieved in a protecting-group-free and redox-economical manner, in only three to four steps starting from l-tryptophan.

1 Introduction

2 Strategic Considerations

2.1 Occurrence of HO-HPIC and HO-aza-HPIC Residues in Natural Products

2.2 Biosyntheses of HO-HPIC and HO-aza-HPIC Residues

2.3 Chemical Syntheses of HO-HPIC and HO-aza-HPIC Residues

3 Procedure-Economical Syntheses of HO-HPIC-Containing Natural Products

3.1 Protecting-Group-Free Syntheses of Asperlicin E, Its Diastereomer, and an Analogue

3.2 Divergent Syntheses of (–)-Robustanoids A and B, a Diastereomer, and Analogues

4 Conclusion and Future Perspectives

Key words

alkaloids - biogenetic hypothesis - biomimetic synthesis - cyclization - divergent synthesis - tandem reaction - total synthesis - umpolung

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