Chemical Constituents From Whitmania Pigra

The animal Whitmania pigra Whitman, which is widely distributed throughout China,belongs to the genus Whitmania in family Haemopidae. The dried material of W. pigra, called“leech” in China, has been used as a Chinese folk medicine for promoting blood circulation andremoving blood stasis. During our search for bioactive natural products, the dried material of W.pigra was investigated.Chemical investigation on the EtOAc and n-BuOH extracts of the95%aqueous ethanolextract from W. pigra led to the isolation of38compounds, including three new pteridines (1-3),a new α-pyrone glycoside (4) and a new natural product (38). The structures of these compoundswere elucidated by spectroscopic techniques, acid hydrolysis, together with ab initio calculations,and they were established as whitmanine A (1), whitmanine B (2),5,8-dimethylleucopterin (3),whitmanoside A (4),(R)-hirudonucleodisulfide B (5), hirudinoidine C (6), hirudinoidine A (7),isolumichrome (8), cyclo(L-Pro-L-Ala)(9), cyclo(L-Pro-L-Val)(10), cyclo(L-Pro-L-Leu)(11),cyclo(L-Pro-L-Pro)(12), cyclo(L-Pro-L-Phe)(13), cyclo(L-Pro-L-Tyr)(14),5-hydroxy-3,4-dimethyl-5-propylfuran-2(5H)-one (15),5-hydroxy-3,4-dimethyl-5-pentylfuran-2(5H)-one (16),liquiritin (17), p-methylphenyl-1-O-β-D-glucopyranoside (18), indole-3-carboxylic acid-β-D-glucopyranosyl (19), indole-3-carboxaldehyde (20), lycoperodine-1(21), adenosine (22),2-hydroxypurine nucleoside (23), uridine (24), adenine (25), uracil (26), xanthine (27),hypoxanthine (28), phenylalanine (29), tyrosine (30), alanine (31), succinic acid (32),p-hydroxybenzoic acid (33), p-hydroxybenzaldehyde (34), phenylacetic acid (35), benzoic acid(36), bisphenol A (37) and2-piperidinone (38). All of these compounds were isolated from aleech for the first time except compounds5-7,28,31and32. In addition, a plausible biosyntheticpathway for the thieno[3,2-g]lumazines in leech was proposed. Xanthosine monophosphate mayserve as the initial starting compound.Compounds1-3,5-8and21-28were evaluated for their inhibitory activity toward thrombin,but none of them showed significant inhibitory effect with IC50values exceeding100μM.