四百五十七章 莫西侧链(1 / 1)

一个星期后,碘普罗胺一百多千克的中试样品交货了,万一有客户要个几千克的大样,供销可随时发货。章海良也出院了,考虑到他的身体状态,调到了办公室与陈总搭档从事项目申报工作。

王近之刚想歇口气,补休几天假,吴总找上门来说:“目前,有个沙星类产品,预估前景相当不错,你组织人员攻关一下。”

研究所就这几粒人,能保证为新厂区设计提供合理的参数,完成工艺文件的编写就相当不错了,那里还有精力新开课题啊,王近之向吴总叫曲道:“或者,你马上给我六七个实验员?”

“实验员下半年会有的,产品研发不能拖,目前,我先把陈骨良调到你部门担任副手。“吴总指了指他身后的眼镜男说:”再给你一个从药厂过来的张淮锦,他正在办离职手续,过几天向你报道。”

莫西沙星的工艺倒不复杂,誓太灵本来就有加替环合酯在生产,拿它与硼酸螯合后,再与莫西侧链侧链(S,S)-2,8-二氮杂双环[4.3.0]壬烷反应就行,可侧链却贵得要命,得上万一千克,吴总通过了中科院下属单位协和大学郭元慧教授的关系搞到了十几克。

张准锦办完手续正式到研究所报到了,他是个老实验员,由面试结果看得出来,做事十分踏实。

莫西沙星的合成路线与加替沙星的高度类似,四天后,王近之、陈骨良与张准锦就打通了合成路线并得到了十几克合格样品,摩尔收率达到91%。可产品成本就在侧链上,高价购买莫西侧链,这个产品就无商业价值,只有自己合成侧链一条道。

郭老师给的侧链(S,S)-2,8-二氮杂双环[4.3.0]壬烷的合成方法是以D-苯甘氨醇为原料来构建其中的手性中心,经过6步反应得到具有手性的六氢吡啶二酸,再经过3步反应制得最终产物。合成路线虽长,但每一步的反应都比较经典,半个月后,路线打通了,可是,这产品最后一步需要用四氢铝锂作为还原剂把酰胺键还原成碳胺键,四氢铝锂的价格得上千元一千克,单耗又大,这么一来,侧链没有个四千元每千克以上的成本拿不下。

“资料报道可以用红铝替代,要不,我们釆购些试一试?”三人带着周飞鸯从浙大寄过来的技术资料逐一分析。

“可是,红铝价格同样贵得要命,浓度又低,副反应多,虽然成本有可能下降,但估算降幅也十分的有限,并且提纯难度大,还有没有其它的报道呢?”王近之的英文不行,对着外文资料两眼一摸黑。

“另外报道就是硼烷还原了,硼烷是一种气体,具体操作没有实施例,估计也只是推导,增加资料的专利保护范围而已。”陈骨良指着专利文献其中的两行文字说。

硼烷还原酰胺与酸,教课书中也常常出现,应当有一定的可行性吧,另外,硼烷用硼氢化钠与酸进行制备,而硼氢化钠尉总这里就在生产,八万多一千克,与硼氢铝锂相比,价格不到它的十分之一。

装置搭起来了,可硼烷是气体,通到回流温度的四氢呋喃中,一会儿就冒出去了,通了三小时后,反应液取样中控,反应倒是进行了,可转化率只有百分之六。

“硼烷有剧毒,通到理论量只转化了这么点儿,成本比硼氢铝锂还要高得多,我们这么搞可不行。”看着探索结果,陈骨良有些灰心。

“有没有关于硼烷还原催化剂方面的报道?加入后可能会好些。”有产物生成了,王近之自然不死心。

资料上只一句话,连操作也没有,那有什么催化剂的报道啊,三人用报道中红铝与四氢铝锂还原的催化剂试了一轮,全部无效。

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