OCA 983 | 161856-02-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: OCA 983
• 英文别名: [1(S),3[4R,5S,6S(R)]]-1-[(2-amino-3-methyl-1-oxobutyl)amino]-2,5-anhydro-3-S-[2-carboxy-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol；(1R,5S,6S)-2-[[(2R,3R)-[[[(S)-2-amino-3-methyl-1-oxobutyl]amino]methyl]tetrahydro-3-furanyl]thio]-6-[(R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid；OCA-983；(4R,5S,6S)-3-[[(2R,3R)-2-[[[(S)-2-amino-3-methyl-1-oxobutyl]amino]methyl]tetrahydro-3-furanyl]thio]-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid；(4R, 5S, 6S)-3-[[(2R, 3R)-2-[[[(S)-2-amino-3-methyl-1-oxobutyl]amino]methyl]tetrahydro-3-furanyl]thio]-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid；(4R,5S,6S)-3-[(2R,3R)-2-[[[(2S)-2-amino-3-methylbutanoyl]amino]methyl]oxolan-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
• CAS: 161856-02-6
• 化学式: C₂₀H₃₁N₃O₆S
• 分子量: 441.549
• InChiKey: AFIMUUSGRZSMCR-LPZKKVOTSA-N

物化性质

• 沸点：
  702.0±60.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  168
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  [1(S),3[4R,5S,6S(R)]]-1-[[[[2-(4-nitrophenyl)methoxy]carbonyl]amino-3-methyl-1-oxobutyl]amino]-2,5-anhydro-3-S-[6-(1-hydroxyethyl)-4-methyl-2-[[(4-nitrophenyl)methoxy]carbonyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]-1,4-dideoxy-3-thio-D-threo-pentitol 在 palladium on activated charcoal 氢气 作用下， 以 1,4-二氧六环 、 phosphate buffer 为溶剂， 反应 5.5h， 以65%的产率得到OCA 983
  参考文献：
  名称：

  口服THF1β-甲基卡巴培南的聚合合成。

  摘要：

  从M2-磷酸酯1开始开发了口服THF1β-甲基卡巴培南4（OCA-983）和5的聚合合成方法。M2-磷酸酯1与含有必需的前药侧链9和10的THF硫醇反应，分别以46％和42％的总收率得到所需的口服THF1β-甲基咔ap烯4和5。

  DOI：

  10.7164/antibiotics.52.643

文献信息

• Convergent Syntheses of Oral THF 1.BETA.-Methylcarbapenems.
  作者：PANAYOTA BITHA、ZHONG LI、YANG-I LIN

  DOI：10.7164/antibiotics.52.643

  日期：——

  Convergent syntheses of oral THF 1beta-methylcarbapenems 4 (OCA-983) and 5 starting from M2-phosphate 1 were developed. Reaction of the M2-phosphate 1 with THF thiols containing a requisite prodrug side chain, 9 and 10, gave the desired oral THF 1beta-methylcarbapenems 4 and 5, respectively, in 46% and 42% overall yields.

  从M2-磷酸酯1开始开发了口服THF1β-甲基卡巴培南4（OCA-983）和5的聚合合成方法。M2-磷酸酯1与含有必需的前药侧链9和10的THF硫醇反应，分别以46％和42％的总收率得到所需的口服THF1β-甲基咔ap烯4和5。
• NOVEL ANTIBACTERIAL AGENTS FOR THE TREATMENT OF GRAM POSITIVE INFECTIONS
  申请人：MetCalf, III Chester A.

  公开号：US20100184649A1

  公开（公告）日：2010-07-22

  The present invention relates to novel lipopeptide compounds, pharmaceutical compositions of these compounds and methods of using these compounds as antibacterial compounds. The compounds of the invention are particularly useful against a variety of bacteria, including resistant strains. The compounds are useful as antibacterial agents against Clostridium difficile.

  本发明涉及新型脂肽化合物，这些化合物的药物组合物以及使用这些化合物作为抗菌化合物的方法。本发明的化合物特别适用于对抗各种细菌，包括耐药菌株。这些化合物可用作抗Clostridium difficile的抗菌剂。
• Process improvement in the preparation of (4R, 5S, 6S)-3-[[(2R,3R)-2-[[[(S)-2-amino-3-methyl-1-oxobutyl]amino]methyl]tetrahydro-3-furanyl]thio]-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid
  申请人：American Home Products Corporation

  公开号：US20020128283A1

  公开（公告）日：2002-09-12

  The invention is a process improvement for producing the carbapenem antibacterial agent (4R, 5S, 6S)-3-[[(2R, 3R)-2-[[[(S)-2-amino-3-methyl-1-oxobutyl]amino]methyl]tetrahydro-3-furanyl]thio]-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid by hydrogenation of 4-nitrobenzyl (4R, 5S, 6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-{[(2R, 3R)-2-({[(2S)-3-methyl-2-({[(4-nitrobenzyl)oxy]carbonyl}amino)butanoyl]amino}methyl)-tetrahydrofuran-3-yl]thio}-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate in a biphasic solvent mixture comprising a water portion and an organic solvent portion, not containing an acid acceptor. Separating the water portion from the organic portion and isolating (4R, 5S, 6S)-3-[[(2R, 3R)-2-[[[(S)-2-amino-3-methyl-1-oxobutyl]amino]methyl]tetrahydro-3-furanyl]thio]-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid from the separated water portion by lyophilization or reverse osmosis.

  这项发明是一种用于生产碳青霉烯抗菌剂(4R, 5S, 6S)-3-[[[(2R, 3R)-2-[[[(S)-2-氨基-3-甲基-1-氧丁基]氨基]甲基]四氢-3-呋喃基]硫]-6-[(R)-1-羟乙基]-4-甲基-7-羟基-1-氮杂双环[3.2.0]庚-2-烯-2-羧酸的工艺改进，通过在由含有水部分和有机溶剂部分组成的两相溶剂混合物中氢化4-硝基苄(4R, 5S, 6S)-6-[(1R)-1-羟乙基]-4-甲基-3-[(2R, 3R)-2-([(2S)-3-甲基-2-([4-硝基苄]氧}羰基)氨基]丁酰氨基}甲基)-四氢呋喃-3-基硫}-7-氧基-1-氮杂双环[3.2.0]庚-2-烯-2-羧酸。将水部分与有机部分分离，并通过冻干或反渗透从分离的水部分中分离出(4R, 5S, 6S)-3-[[[(2R, 3R)-2-[[[(S)-2-氨基-3-甲基-1-氧丁基]氨基]甲基]四氢-3-呋喃基]硫]-6-[(R)-1-羟乙基]-4-甲基-7-羟基-1-氮杂双环[3.2.0]庚-2-烯-2-羧酸。
• Novel Lipopeptides as Antibacterial Agents
  申请人：Hill Jason

  公开号：US20090011977A1

  公开（公告）日：2009-01-08

  The present invention relates to novel lipopeptide compounds. The invention also relates to pharmaceutical compositions of these compounds and methods of using these compounds as antibacterial compounds. The invention also relates to methods of producing these novel lipopeptide compounds and intermediates used in producing these compounds.

  本发明涉及新型脂肽化合物。本发明还涉及这些化合物的药物组合物以及将这些化合物用作抗菌化合物的方法。本发明还涉及生产这些新型脂肽化合物的方法以及用于生产这些化合物的中间体。
• PROCESS IMPROVEMENT IN THE PREPARATION OF (4R, 5S, 6S)-3-[[(2R,3R)-2-[[[(S)-2-AMINO-3-METHYL-1-OXOBUTYL]AMINO]METHYL]TETRAHYDRO-3-FURANYL]THIO]-6-[(R)-1-HYDROXYETHYL]-4-METHYL-7-OXO-1-AZABICYCLO[3.2.0]HEPT-2-ENE-2-CARBOXYLIC ACID
  申请人：Wyeth, Five Giralda Farms

  公开号：US06649756B2

  公开（公告）日：2003-11-18

  The invention is a process improvement for producing the carbapenem antibacterial agent (4R, 5S, 6S)-3-[[2R,3R)-2-[[[(S)-2-amino-3-methyl-1-oxobutyl]amino]methyl]tetrahydro-3-furanyl]thio]-6-[R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid by hydrogenation of 4-nitrobenzyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-{[2R,3R)-2-({[(2S)-3-methyl-2-({[4-nitrobenzyl)oxy]carbonyl}amino)butanoyl]amino}methyl)-tetrahydrofuran-3-yl]thio}-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate in a biphasic solvent mixture comprising a water portion and an organic solvent portion, not containing an acid acceptor. The water portion is separated from the organic solvent portion and (4R,5S,6S)-3-[[(2R,3R)-2-[[[(S)-2-amino-3-methyl-1-oxobutyl]amino]methyl]tetrahydro-3-furanyl]thio]-6-[R-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid is isolated from the separated water portion by lyophilization or reverse osmosis.

  这项发明是一种生产碳青霉烯类抗菌剂(4R,5S,6S)-3-[[(2R,3R)-2-[(S)-2-氨基-3-甲基-1-氧丁基]氨基]-甲基]-四氢呋喃-3-基硫代-6-[(R)-1-羟乙基]-4-甲基-7-氧代-1-氮杂双环[3.2.0]庚-2-烯-2-羧酸的改进工艺，通过在不含酸受体的两相溶剂混合物中将4-硝基苄基(4R,5S,6S)-6-[(1R)-1-羟乙基]-4-甲基-3-[[[(2R,3R)-2-[[(2S)-3-甲基-2-[(4-硝基苄基)氧]羰基]氨基]丁酰]氨基]甲基]-四氢呋喃-3-基硫代-7-氧代-1-氮杂双环[3.2.0]庚-2-烯-2-羧酸酯氢化而得。将水相与有机溶剂相分离，从分离出的水相中通过冻干或反渗透法分离出(4R,5S,6S)-3-[[(2R,3R)-2-[(S)-2-氨基-3-甲基-1-氧丁基]氨基]-甲基]-四氢呋喃-3-基硫代-6-[(R)-1-羟乙基]-4-甲基-7-氧代-1-氮杂双环[3.2.0]庚-2-烯-2-羧酸。