(3S,4S)-3-amino-1-(2,4-dimethoxybenzyl)-4-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)azetidin-2-one | 86334-58-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (3S,4S)-3-amino-1-(2,4-dimethoxybenzyl)-4-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)azetidin-2-one
• 英文别名: (3S,4S)-cis-3-amino-1-(2,4-dimethoxybenzyl)-4-[(R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-azetidinone；(3S,4S)-3-amino-1-(2,4-dimethoxybenzyl)-4-[(R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-azetidinone；(3S,4S)-3-amino-1-[(2,4-dimethoxyphenyl)methyl]-4-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]azetidin-2-one
• CAS: 86334-58-9
• 化学式: C₁₇H₂₄N₂O₅
• 分子量: 336.388
• InChiKey: GMCHABHPTSSRPS-SOUVJXGZSA-N

物化性质

• 沸点：
  508.4±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  83.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S,4S)-3-amino-1-(2,4-dimethoxybenzyl)-4-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)azetidin-2-one 在 sodium tetrahydroborate 、 sodium periodate 、 碳酸氢钠 、 对甲苯磺酸 、 lithium chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 6.5h， 生成 benzyl ((2S,3S)-1-(2,4-dimethoxybenzyl)-2-(hydroxymethyl)-4-oxoazetidin-3-yl)carbamate
  参考文献：
  名称：

  合成单杆菌素LYS228的工艺开发

  摘要：

  已经开发出可扩展的新型单杆菌素抗生素LYS228的方法。本文介绍了一种新颖的可扩展工艺，用于生产多千克规模的β-内酰胺10。已证明无需保护基交换的化合物7的替代方法可缩短合成时间。进行了侧链20的可扩展过程，该过程使用替代试剂来减轻初始医学化学方法带来的安全风险。最终组装成稳定的隔离产品LYS228，并以千克为单位进行了组装。

  DOI：

  10.1021/acs.oprd.9b00330
• 作为产物：
  描述：

  L-甘油醛缩丙酮 在 氯化亚砜 、 一水合肼 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 8.66h， 生成 (3S,4S)-3-amino-1-(2,4-dimethoxybenzyl)-4-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)azetidin-2-one
  参考文献：
  名称：

  合成单杆菌素LYS228的工艺开发

  摘要：

  已经开发出可扩展的新型单杆菌素抗生素LYS228的方法。本文介绍了一种新颖的可扩展工艺，用于生产多千克规模的β-内酰胺10。已证明无需保护基交换的化合物7的替代方法可缩短合成时间。进行了侧链20的可扩展过程，该过程使用替代试剂来减轻初始医学化学方法带来的安全风险。最终组装成稳定的隔离产品LYS228，并以千克为单位进行了组装。

  DOI：

  10.1021/acs.oprd.9b00330

文献信息

• MONOBACTAM ORGANIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS
  申请人：AULAKH Virender Singh

  公开号：US20150266867A1

  公开（公告）日：2015-09-24

  This invention pertains generally to antibacterial compounds of Formula I, as further described herein, and pharmaceutically acceptable salts and formulations thereof. In certain aspects, the invention pertains to methods of using such compounds to treat infections such as those caused by Gram-negative bacteria.

  这项发明通常涉及公式I的抗菌化合物，如本文进一步描述，并其药用盐和制剂。在某些方面，该发明涉及使用这些化合物治疗由革兰氏阴性细菌引起的感染的方法。
• Process for the manufacture of 1-sulpho-2-oxoazetidine carboxylic acid
  申请人：Hoffmann-La Roche Inc.

  公开号：US04652651A1

  公开（公告）日：1987-03-24

  The manufacture of 1-sulpho-2-oxazetidine derivatives of the formula ##STR1## in which Het is an optionally amino-substituted, 5- or 6-membered, aromatic heterocycle containing 1 or 2 nitrogen atoms and optionally also an oxygen or sulphur atom, R.sup.1 is hydrogen, lower alkyl, phenyl-lower alkyl, lower alkanoyl, lower alkoxycarbonyl, lower alkenyl-lower alkyl, lower alkoxycarbonyl-lower alkyl, phenyl-lower-alkoxycarbonyl-lower alkyl, nitrophenyl-lower-alkoxycarbonyl-lower alkyl or carboxy-lower alkyl and R.sup.2 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, lower alkoxycarbonyl, lower alkanoyloxy-lower alkyl, lower alkoxycarbonyl-lower alkenyl, hydroxyiminomethyl, lower alkoxyiminomethyl, carbamoyl, carbamoyl-lower alkenyl or carbamoyloxy-lower alkyl, the group .dbd.NOR.sup.1 being present at least partially in the syn-form, in racemic form or in the form of the 3S-enantiomer, and of readily hydrolyzable esters and pharmaceutically compatible salts of these compounds, by acylating a compound of the formula ##STR2## in which R.sup.20 equals R.sup.2 or can also represent a 2,2-dimethyl-1,3-dioxolan-4-yl group and R.sup.3 is hydrogen or sulpho, or a salt thereof with a thioester of the formula ##STR3## in which Het is as above and R.sup.10 has any of the values of R.sup.1 except carboxy-lower alkyl, and can also represent a tri-lower alkyl-silyl-lower-alkoxycarbonyl-lower alkyl group or a carboxy-lower alkyl group converted into a readily hydrolyzable ester group, and the group .dbd.NOR.sup.10 is present at least partially in the syn-form, and carrying out subsequent steps (N-sulphonation, conversion of R.sup.20 into R.sup.2, R.sup.10 into R.sup.1), some of which are optional. The invention also provides certain novel products of formula I and benzthiazolyl thioesters of formula III per se and the preparation of the benzthiazolyl thioesters by esterifying corresponding carboxylic acids. Finally, the invention provides a process for the preparation of carboxylic acids in which R.sup.1 is t-alkoxycarbonylmethyl. The compounds of formula I have antimicrobial activity.

  该专利描述了一种制备1-磺酸-2-噁唑环丙烷衍生物的方法，其化学式为##STR1##其中Het是一个含有1或2个氮原子和可能还有一个氧原子或硫原子的可选氨基取代的5或6元芳香杂环，R.sup.1是氢、低烷基、苯基-低烷基、低烷酰、低烷氧羰基、低烯基-低烷基、低烷氧羰基-低烷基、苯基-低烷氧羰基-低烷基、硝基苯基-低烷氧羰基-低烷基或羧基-低烷基，R.sup.2是氢、低烷基、低烯基、低炔基、低烷氧羰基、低烷酰氧基-低烷基、低烷氧羰基-低烯基、羟基亚胺甲基、低烷氧亚胺甲基、氨甲酰基、氨甲酰基-低烯基或氨甲酰氧基-低烷基，.dbd.NOR.sup.1基团至少部分以syn-形式存在，是外消旋形式或3S-对映体形式，以及这些化合物的易水解酯和药用兼容盐的制备方法。
• Antimicrobial 2-oxo-1-azetidinesulphonic acids
  申请人：Hoffmann-La Roche Inc.

  公开号：US04816582A1

  公开（公告）日：1989-03-28

  Antimicrobial 2-oxo-1-azetidinesulphonic acids of the formula ##STR1## in which H.sub.2 N ##STR2## represents an amino-substituted thiazolyl group, R.sup.1 is lower alkyl which is substituted by carbamoyl, lower alkylsuphonyl, azido, piperidine-carbonyl, (hexahydro-1H-azepin-1-yl)carbonyl or lower alkynyl, and R.sup.2 is hydrogen or a lower organic group, typically, carbamoyloxymethyl.

  公式为##STR1##的抗微生物2-氧代-1-氮杂环丙磺酸，其中H.sub.2 N ##STR2##代表氨基取代的噻唑基团，R.sup.1是被氨甲酰基、低烷基磺酰基、叠氮基、哌啶基甲酰基、(六氢-1H-氮杂环庚烯-1-基)甲酰基或低烷基炔基取代的低烷基，R.sup.2是氢或低有机基，通常为氨甲酰氧甲基。
• .beta.-Lactams
  申请人：Hoffman-La Roche Inc.

  公开号：US04576751A1

  公开（公告）日：1986-03-18

  There is presented optically uniform .beta.-lactams of the formulae ##STR1## wherein Z is a readily cleavable acyl group, R.sup.1 is amino or a group convertible into amino, R.sup.2 is hydrogen or a readily cleavable protecting group and R.sup.3 and R.sup.4 each are a lower hydrocarbon group which optionally contains oxygen and which is attached via a carbon atom, whereby these groups can also be joined with one another to form a ring, with the proviso that R.sup.1 is a readily cleavable acylamino when R.sup.2 is hydrogen, and the corresponding optical antipodes, their manufacture and use in the manufacture of antimicrobially-active .beta.-lactams as well as novel intermediates usable in their manufacture.

  提供了光学均匀的β-内酰胺，其结构式如下：其中Z是易于水解的酰基，R.sup.1是氨基或可转化为氨基的基团，R.sup.2是氢或易于水解的保护基团，R.sup.3和R.sup.4分别是低碳氢基团，可选地含氧，并通过碳原子连接，这些基团也可以相互连接形成环，但R.sup.1是易于水解的酰胺基团当R.sup.2为氢时，以及相应的光学对映体，它们的制造和用于制造抗微生物活性的β-内酰胺以及在其制造中可用的新型中间体。
• An Enantioselective ?-Lactam Synthesis Starting fromL-(S)-Glyceraldehyde Acetonide
  作者：Christian Hubschwerlen、G�rard Schmid

  DOI：10.1002/hlca.19830660732

  日期：1983.11.2

  Complete diastereoselectivity is observed during the cyclocondensation of activated glycine derivatives with aldimines derived from L-(S)-glyceraldehyde acetonide. 3,4-cis-β-lactams are isolated in high optical and chemical yields. They are converted into key intermediates used in the syntheses of various mono- and bicyclic β-lactam antibiotics. A mechanism is suggested to explain this remarkable

  在活化的甘氨酸衍生物与衍生自L- （S） -甘油醛丙酮化物的醛亚胺的环缩合过程中观察到完全的非对映选择性。以高光学和化学收率分离出3，4-顺-β-内酰胺。它们被转化为用于合成各种单环和双环β-内酰胺抗生素的关键中间体。建议一种机制来解释这种非对映选择性。