Structure–activity relationship studies on acremomannolipin A, the potent calcium signal modulator with a novel glycolipid structure 3: Role of the length of alditol side chain

• Published in: Bioorganic & medicinal chemistry Vol. 23; no. 13; pp. 3761 - 3773
• Main Authors: Tsutsui, Nozomi, Tanabe, Genzoh, Morita, Nao, Okayama, Yoshitomo, Kita, Ayako, Sugiura, Reiko, Muraoka, Osamu
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.07.2015; Elsevier
• Subjects: Acremomannolipin A; Acremonium - chemistry; Acremonium strictum; Biochemistry & Molecular Biology; Calcineurin - deficiency; Calcineurin - genetics; Calcium - metabolism; Calcium Channel Agonists - chemical synthesis; Calcium Channel Agonists - isolation & purification; Calcium Channel Agonists - pharmacology; Calcium signal modulator; Calcium Signaling; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Expression; Glycolipid; Glycolipids - chemical synthesis; Glycolipids - isolation & purification; Glycolipids - pharmacology; Ion Transport; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; SAR study; Schizosaccharomyces - drug effects; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Science & Technology; Structure-Activity Relationship; Sugar Alcohols - chemistry; Acremomannolipin A; Calcium signal modulator; SAR study; Acremonium strictum; Glycolipid; BETA-MANNOPYRANOSIDES; ANALOGS; FUNGUS ACREMONIUM-STRICTUM
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2015.03.079

[Display omitted] Five homologs of a novel glycolipid acremomannolipin A (1a), the potential Ca2+ signal modulator isolated from Acremonium strictum, bearing alditols of different length (1g–1k) were synthesized by a stereoselective β-mannosylation of appropriately protected mannosyl sulfoxide (2) with five alditols (1g: C2, 1h: C3, 1i: C4, 1j: C5 and 1k: C7 units), and their potential in modulating Ca2+ signaling were evaluated. Homologs with alditols of more than 4 carbons (1i, 1j and 1k) were equally or more potent than the parent compound (1a) regardless of the length of the alditol chain. Whereas activities of two homologs with shorter chains (1g and 1h) decreased to a considerable extent. The results indicated that the length of the alditol side chain was a crucial determinant for the potent calcium signal modulating activity.