Total synthesis of CRM646-A and -B, two fungal glucuronides with potent heparinase inhibition activities.
[reaction: see text] CRM646-A (1) and -B (2), two fungal glucuronides with a dimeric 2,4-dihydroxy-6-alkylbenzoic acid (orcinol p-depside) aglycone showing significant heparinase and telomerase inhibition activities, were synthesized for the first time. The successful approach involved construction of the phenol glucuronidic linkage, via coupling of the orsellinate derivative 27 with glucuronate bromide 7, before assembly of the phenolic ester linkage in the depside aglycone. Attempts via direct glycosylation of the depside aglycone derivatives were not successful.
Wang
Ping
P
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.
Zhang
Zhaojun
Z
Yu
Biao
B
D000164:Acremonium / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019763:Heparin Lyase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062385:Hydroxybenzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D010084:Oxidation-Reduction
C408433:CRM646 A; C408434:CRM646 B; D004791:Enzyme Inhibitors; D062385:Hydroxybenzoates; D019763:Heparin Lyase