Synthetic study of leonurine and its analogues

by Yip, Che-shing

(Uncorrected OCR) Abstract of thesis entitled "Synthetic Study of Leonurine and its Analogues" submitted by Yip Che Shing for the degree of Master of Philosophy at the University of Hong Kong in October, 1978.

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ABSTRACT

Leonurine 1, isolated from Leonurus sibiricus and a .

Leonurus artemisia, was found to have uterotonic effect.

Ther~fore leonurine 2 and some of its analogues were

synthesized for pharmaceutical study.

An efficient, two-step synthesis of leonurine 3 from

syringic acid 1 and 4-amino-l-butanol 16 is described. The amino alcohol ~ was treated with S-benzyl-iso-

thiourea hydrochloride 65 affording 4-guanidino-l-butanol

hydrochloride l. Direct condensation of syringic acid 1

and 2 in the presence of DCe in HMPT or 1:1 HMPT-ether

gave in high yield of leonurine 3 which was identical in

all respect with the natural leonurine isolated from

Leonurus atemisia.

This direct condensation of carboxylic acid' and alcohol

was extended to the synthesis of the following leonurine

analogues - twelve guanidinoalkyl esters, twenty-two

aminoalkyl esters, two imidazoylalkyl esters. and three

ureidoalkyl esters.

The effect of~phenolic group in the carboxylic acids

on the DeC promoted ester condensatio~ in HMPT as solvent

is discussed.

Synthesis of amino esters was achieved either by direct

condensation ofo..carboxylic acid wi th r~spec.tlv.e.;" protonated .~

amino alcohols in the presence of DCC, or by reaction of

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carboxylic acid and chloroalkylamine in triethylamine. The yield of aminoalkyl esters synthesized by these two methods

were compared.

The mass spectra of leonurine 3 and its guanidino

analogues were analysed.