Flindersia alkaloids, derivatives and analogs: compositions and methods for producing the same

Patent metadata

Field	Value
Publication number	US-9353109-B2
Application number	US-201514753480-A
Country	US
Kind code	B2
Filing date	Jun 29, 2015
Priority date	Jan 19, 2012
Publication date	May 31, 2016
Grant date	May 31, 2016

Abstract

The present invention provides methods for chemically synthesizing analogs and derivatives of naturally-occurring Flindersia alkaloids. Generally, the precursor borrerine is synthesized from tryptamine in the presence of an alkylating agent, an acylating agent and a reducing agent and dimerized in the presence of an acid, for example, trifluoroacetic acid, hydrochloric acid or acetic acid to yield the products. Analog and derivative compounds are produced by derivatizing one or more of the tryptamine, alkylating agent or acylating agent. Also provided are the synthetic alkaloids and derivatives and analogs thereof produced by the synthetic methods.

First claim

What is claimed is:

1. A method for chemically synthesizing an analog of dimethylisoborreverine, comprising the steps of:
adding an alkylating agent to tryptamine derivatized independently at one or more of C4, C5, C6, and C7 with hydroxy, methoxy, acetoxy, benzyloxy, sulfomethyl, amino, acetate, methyl, ethyl, iso-propyl, t-butyl, trifluoromethyl, cyano, methylformate, nitrate, or halide;
adding an acylating agent in the presence of a base to form a substituted piperidinyl-N-carbamate intermediate;
adding a strong reducing agent to the intermediate to produce a borrerine derivative;
methylating the borrerine derivative with a methylating agent;
dimerizing the methylated borrerine derivative in the presence of trifluoroacetic acid to yield the dimethylisoborreverine analog.

2. The method of claim 1 , wherein the alkylating agent is 3-methyl 2-butenal, the acylating agent is methyl chloroformate and the strong reducing agent is lithium aluminum hydride.

3. The method of claim 1 , wherein the base is pyridine.

4. The method of claim 1 , wherein the methylating agent is methyl triflate or dimethyl sulfate.

5. A chemical synthetic method for producing dimethylisoborreverine, comprising the steps of:
synthesizing borrerine from tryptamine;
methylating the synthesized borrerine; and,
dimerizing the methylated intermediate in the presence of trifluroacetic acid to yield dimethylisoborreverine.

6. The method of claim 5 , wherein the synthesizing step comprises:
adding 3-methyl 2-butenal to tryptamine;
adding methyl chloroformate in the presence of a base to form a substituted piperidinyl-N-carbamate intermediate; and
adding a strong reducing agent to the intermediate to produce borrerine.

7. The method of claim 6 , wherein the base is pyridine.

8. The method of claim 6 , wherein the reducing agent is lithium aluminum hydride.

9. The method of claim 5 , wherein the methylating agent is methyl triflate or dimethyl sulfate.

Assignees

• May Jeremy A
• Vallakati Ravikrishna
• Univ Houston System

Inventors

• May Jeremy A
• Vallakati Ravikrishna

Classifications

• C07D471/06

  Peri-condensed systems · CPC title

• A61P33/06

  Antimalarials · CPC title

• C07D487/08

  Bridged systems · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D487/06

  Peri-condensed systems · CPC title