新型含氮麦芽寡糖、α-淀粉酶抑制剂的合成及其生物活性。

Synthesis of new N-containing maltooligosaccharides, alpha-amylase inhibitors, and their biological activities.

作者信息

Uchida R, Nasu A, Tokutake S, Kasai K, Tobe K, Yamaji N

机构信息

Research and Development Division, Kikkoman Corporation, Chiba, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1999 Feb;47(2):187-93. doi: 10.1248/cpb.47.187.

DOI:10.1248/cpb.47.187

PMID:10071853

Abstract

Fifteen new N-containing maltooligosaccharides were obtained using the chemoenzymatic method. Among these compounds, maltooligosaccharides having 6-amino-6-deoxy-D-sorbitol residue, (3R,4R,5R,6S)-hexahydro-3,4,5,6-tetrahydroxy-1H-azepine residue, and (3R,5R)-3,4,5-trihydroxypiperidine residue at the reducing end showed strong inhibitory activities for human pancreatic alpha-amylase (HPA) (EC 3.2.1.1) and human salivary alpha-amylase (HSA). The administration of (3R,4R,5R,6S)-hexahydro-3,5,6-trihydroxy-1H-azepine-4-yl O-alpha-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranoside (13, IC50 = 4.3 x 10(-5) M for HPA, IC50 = 8.2 x 10(-5) M for HSA) and (3R,5R)-3,5-dihydroxypiperidine-4-yl O-alpha-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranoside (18, IC50 = 3.4 x 10(-5) M for HPA, IC50 = 4.6 x 10(-5) M for HSA) to ICR mice suppressed postprandial hyperglycemia.

摘要

采用化学酶法获得了15种新的含氮麦芽寡糖。在这些化合物中，还原端具有6-氨基-6-脱氧-D-山梨醇残基、(3R,4R,5R,6S)-六氢-3,4,5,6-四羟基-1H-氮杂环庚烷残基和(3R,5R)-3,4,5-三羟基哌啶残基的麦芽寡糖对人胰腺α-淀粉酶（HPA）（EC 3.2.1.1）和人唾液α-淀粉酶（HSA）表现出较强的抑制活性。给ICR小鼠施用(3R,4R,5R,6S)-六氢-3,5,6-三羟基-1H-氮杂环庚烷-4-基O-α-D-吡喃葡萄糖基-(1→4)-α-D-吡喃葡萄糖苷（13，对HPA的IC50 = 4.3×10⁻⁵ M，对HSA的IC50 = 8.2×10⁻⁵ M）和(3R,5R)-3,5-二羟基哌啶-4-基O-α-D-吡喃葡萄糖基-(1→4)-α-D-吡喃葡萄糖苷（18，对HPA的IC50 = 3.4×10⁻⁵ M，对HSA的IC50 = 4.6×10⁻⁵ M）可抑制餐后高血糖。