{'fraction_non_alphanumeric': 0.03433922996878252, 'fraction_numerical': 0.022892819979188347, 'mean_word_length': 5.127388535031847, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
First Synthesis of Argadin: A Nanomolar Inhibitor of Family‐18 Chitinases

The first synthesis of the cyclic peptide natural product, argadin is reported. Use of a solid-phase approach featuring side-chain resin attachment through histidine and a novel protecting group strategy allows rapid and efficient access to the argadin backbone, whereupon the unusual 3-amino-5-hydroxy-2-pyrrolidone moiety of the peptide is introduced by oxidative cyclisation of a homoserine residue. Argadin is shown to exist as a 5:1 mixture of diastereoisomers at the 5-hydroxy centre of the pyrrolidone ring, and inhibits a representative family-18 chitinase (ChiB1 from Aspergillus fumigatus) with Ki = 33 nM. The high-resolution X-ray crystal structure of synthetic argadin in complex with the same enzyme shows the binding of a single diastereoisomer as previously observed with the authentic natural product. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)