1-脱氧野尻霉素的来源及合成研究进展

Research Progress in Origin and Synthesis of 1-Deoxynojirimycin

1-脱氧野尻霉素(1-deoxynojirimycin,DNJ)是一种有效的α-糖苷酶抑制剂,具有显著的降血糖作用。野尻霉素最先从链霉菌中发现,而天然DNJ最先是从桑根皮中分离到的。在植物中,已从桑树(MorusL.)、鸭跖草(Commelina communis)、风信子(Hyacinthus orientalis)以及沙参属植物(Adenophora triphyllavar.japonica)中分离鉴定到DNJ,其中桑树中的DNJ含量最高,并且因桑品种、药用部位、季节气候、地理土壤、叶位和发育阶段等因素的不同而存在很大差异。在微生物中,已从多种链霉菌和芽孢杆菌中分离到DNJ,还发现从桑树中分离到的嗜麦芽寡养假单胞杆菌(Stenotrophomonas maltophilia)和藤黄微球菌(Micrococcus luteus)2种内生菌也能够产生DNJ,已对多种微生物产DNJ的发酵条件进行研究。在昆虫中,除家蚕(Bombyxmori)富含DNJ外,野桑蚕(Bombyxmandarina)、桑蟥(Rondotia menciana)、桑尺蠖(Phthonandria atrineata)、桑螟(Diaphani apy-loalis)等取食桑叶的单食性或寡食性昆虫也富含DNJ,昆虫体内的DNJ来源于食物,其中家蚕体内DNJ的含量因蚕品种、发育时期、组织器官以及饲料等因素的不同而异,家蚕随龄期进展存在着对DNJ的吸收富集和排泄的周期性变化。目前已经对链霉菌、芽孢杆菌和鸭跖草体内DNJ的生物合成途径进行了探索,发现不同物种体内DNJ的合成机制不同。另已探明了DNJ的3种主要合成方法,人工合成的一些DNJ衍生物已经应用于临床。

1-Deoxynojirimycin （DNJ） is an effective α-glucosidase inhibitor, being able to lower blood glucose efficiently. Nojirimycin was firstly found in streptomyces, while DNJ was firstly isolated from the root bark of mulberry tree. DNJ has been isolated and identified from mulberry （ Morus L. ）, dayflower （ Commelina communis）, hyacinth （ Hyacinthus orientalis） and adenophora （Adenophora triphylla var. japonica）, among which mulberry has the highest content of DNJ. DNJ content of mulberry varies greatly with mulberry varieties, medicament portions, seasons, climates, geo- graphical and soil conditions, leaf positions, and development stages etc. In microorganisms, DNJ was isolated from various species of streptomycete and bacillus. It was also discovered that two endophytes from mulberry, Stenotroph- omonas maltophilia and Micrococcus luteus, could produce DNJ stably. So far, fermentation conditions for many micro- organisms with DNJ production have been investigated. In insect, besides silkworm （ Bombyx mori） which has rich con-tent of DNJ, other mulberry monophagous insect species or oligophagous ones including Bombyx mandarina, Rondotia menciana, Phthonandria atrineata, and Diapha- ni apyloalis also have high content of DNJ. DNJ in insect body comes from their food, and DNJ content in silkworm body varies with silkworm species, developmental peri-ods, diet, tissue and organ etc. It was also noticed that absorption and concentration of DNJ in silkworm body changed periodically with the advance of larval instar. Researches aiming to elucidate biosynthetic pathway of DNJ in streptomyce- re, bacillus, and dayfiower have been conducted. It was found that DNJ synthetic pathway is different in different spe- cies. Important progress has been made in chemosynthesis of DNJ. Three major synthetic methods have been devel- oped and some synthesized DNJ derivatives have .been used in clinir.