A synthesis of tiruchanduramine and a reinvestigation of its glycosidase inhibitory activity

Synthesis of (+)-(R)-Tiruchanduramine

“…Reduction of the mixed anhydride of 12 with sodium borohydride gave alcohol 13 in an 86% yield [11]. Deprotection of 13 using piperidine in dichloromethane gave the amine 14 which was guanidinylated [1] with 15 to give the alcohol 16 in 94% yield. Cyclization of this with a mixture of I 2 /dppe/PPh 3 /imidazole [1] in dichloromethane to give the cyclic guanidine 17 which was used in the next steps without purification as it was found to undergo decomposition on silica gel.…”

“…Deprotection of 13 using piperidine in dichloromethane gave the amine 14 which was guanidinylated [1] with 15 to give the alcohol 16 in 94% yield. Cyclization of this with a mixture of I 2 /dppe/PPh 3 /imidazole [1] in dichloromethane to give the cyclic guanidine 17 which was used in the next steps without purification as it was found to undergo decomposition on silica gel. Crude 17 was deprotected using aqueous HCl (3M) and after freeze drying gave the desired guanidine (R)-5.…”

“…We have previously reported [1] a racemic synthesis of the alkaloid tiruchanduramine 1 (Figure 1) isolated by Ravinder et al [2] from the ascidian Synoicum macroglossum and shown to be a α-glucosidase inhibitor. Glucosidases have a number of roles in the body, including digestion, glycoprotein processing and degradation, and have differing locations and substrate specificities [3].…”

“…Amide 4 was converted into the hydrochloride salt of 1 via a four-step protocol involving the introduction of the guanidine under Mitsunobu conditions (Scheme 1). Our racemic synthesis [1] differed from this as it was a convergent approach in which the guanidine heterocycle 5 is prepared separately then coupled to the β-carboline-3-carboxylic acid 2 (Scheme 1). and shown to be a α-glucosidase inhibitor.…”

Isolation and Characterization of Antimicrobial Peptides with Unusual Disulfide Connectivity from the Colonial Ascidian Synoicum turgens

“…As part of our ongoing search for new compounds with antimicrobial activity from marine invertebrates, the aqueous extract of the colonial ascidian Synoicum turgens was examined for its content of AMPs. Synoicum species have previously awarded several bioactive secondary metabolites, including the cytotoxic palmerolide macrolides [30,31], the β-carboline guanidine alkaloid tiruchanduramine with α-glucosidase inhibitory activity [32,33], and the synoxazolidinones and pulmonarines with various bioactivities from S. pulmonaria [34][35][36][37]. To the best of our knowledge, no AMPs have been isolated and characterized from Synoicum species.…”