Modified pictet-spengler reaction and products prepared therefrom

Abstract

A method of introducing a second stereogenic center into a tetrahydro-β-carboline have two stereogenic centers using a modified Pictet-Spengler reaction is disclosed. The method provides a desired cis- or trans-isomer in high yield and purity, and in short processes times.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a modified Pictet-Spengler reaction for introducing a second stereogenic center into a compound. More particularly, the present invention relates to a modified Pictet-Spengler reaction that provides a desired cis- or trans-diastereomer of a polycyclic compound having two stereogenic centers, in high yield and high purity.BACKGROUND OF THE INVENTION[0002]Compounds that exhibit biological activity typically contain at least one asymmetric carbon atom, i.e., at least one choral center. A particular stereoisomer of such a compound usually exhibits excellent biological activity, whereas the other stereoisomers exhibit no or little biological activity. Accordingly, investigators strive to synthesize the biologically active stereoisomer, while minimizing or eliminating synthesis of the inactive or less active stereoisomer.[0003]Stereochemical purity is important in the pharmaceutical field, where many of the most often prescribed...

AI Technical Summary

Benefits of technology

[0015]Prior investigators attempted to prepare a desired diastereomer of a polycyclic ring system containing two asymmetric ring carbon atoms by performing a Pictet-Spengler cyclization reaction. These attempts generally were limited in success because the reaction was performed in a corrosive medium, led to mixtures of diastereomers that adversely affected reaction yield, and required several days to perform. The present method provides the desired diastereomer in good yield and short reaction times, and avoids the use of TFA.

[0017]Another aspect of the present invention is to increase the yield of the desired diastereomer by allowing the undesired diastereomer to equilibrate in solution to provide additional desired diastereomer that precipitates from solution, and thereby increase the yield of the desired diastereomer at the expense of the undesired diastereomer.

Problems solved by technology

These attempts generally were limited in success because the reaction was performed in a corrosive medium, led to mixtures of diastereomers that adversely affected reaction yield, and required several days to perform.

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