烯醇化

Then Doripenem came into the market in the July ,2005. We studied the synthesis of Doripemen.Firstly, we synthesized the chemical 2 from the starting material------o-hydroxylphenylacylamine through Reformastky reaction, alkylation, Diekmann reaction, enolization, esterification and etc. Secondly, we synthesized the chemical 3 from L — hydroxylproline through the protection of carboxyl, amidogen and hydroxyl group, reduction by NaBr, SN_2 substitution and Mitsumobu reaction.

我们以水杨酰胺为起始原料，经Reformatsky反应、烷基化、Diekmann环合、烯醇化、酯化等反应合成双环母核2；再从L-羟基脯氨酸出发，经酯化保护羧基、保护氨基、保护羟基、硼氢化还原酯得醇、Sn2取代和Mitsumobu反应等合成巯基侧链3；最后由化合物3经脱保护、水解得硫醇，和化合物2在二异丙基乙基胺的作用下缩合，最后Pd／C催化脱保护，历经16步反应最终得到产物多尼培南。

It was shownthat, among the three possible tautomers; i.e., the keto-form and the two enol forms, and thecorresponding enol anion, only the enol form 31 was actually responsible for the singletoxygen reactions.

用核磁共振及从头算法研究了化合物12b和23a在甲醇和吡啶中的烯醇化作用，结果表明，在其三种互变异构体以及相应烯醇负离子中，只有烯醇式31是实际参与单重态氧反应的成份。

Phosphoglycerate is converted to 2-phosphoglycerate by phosphoglycerate mutase.

2-磷酸甘油酸在烯醇化酶的催化下生成磷酸烯醇式丙酮酸。

From the femur bone density analysis of protein expression, we can see that light chain lactoferrin, annexin decreased and the expression of enolase, ATP synthase, acetyl-coenzyme A reductase, the expression of troponin, may be related to ovariectomized femoral bone density in osteoporosis-related happened; strong bone of the femoral osteoporosis Po intervention effect may be related to reduced enolase, ATP synthase, troponin, CK-MB, acetyl phosphoglycerate enzyme, the expression of myosin, and the increase in lactoferrin light chain, pyruvate kinase isoenzyme, protein expression crown.

从股骨密质骨蛋白质组表达分析可知，乳铁蛋白轻链、膜联蛋白A3的表达下降及烯醇化酶、ATP合酶、乙酰辅酶A还原酶、肌钙蛋白的表达增强，可能与去卵巢后股骨密质骨骨质疏松的发生相关；强骨宝对股骨骨质疏松的干预效应可能与下调烯醇化酶、ATP合酶、肌钙蛋白、肌酸激酶同工酶、磷酸甘油酸变味酶、肌球蛋白的表达，和上调乳铁蛋白轻链、丙酮酸激酶同工酶、冠蛋白的表达有关。

Cancellous bone from the lumbar proteomic expression analysis show that actin, keratin, enolase, ATP synthase, the expression of myosin may be related to ovarian lumbar cancellous bone after osteoporosis-related happened; Qiang Gu Bao Po on the lumbar spine osteoporosis intervention effect may be related to reduced carbonic anhydrase, actin, crystal protein, 3- phosphoglycerate dehydrogenase, serum albumin, ATP synthase, myosin, the enolase expression.

从腰椎松质骨蛋白质组表达分析可知，肌动蛋白、角蛋白、烯醇化酶、ATP合酶、肌球蛋白的表达增强可能与去卵巢后腰椎松质骨骨质疏松的发生相关；强骨宝对腰椎骨质疏松的干预效应可能与下调碳酸酐酶、肌动蛋白、αB-晶体蛋白、3-磷酸甘油醛脱氢酶、血清白蛋白、ATP合酶、肌球蛋白、烯醇化酶的表达有关。

Second, using DBU as the base for enolization of propargylic esters of unsaturated acids 18e-k, we developed a tandem Ireland-Claisen rearrangement /isomerization reactions. It has been shown that the reaction sequence affords triene molecules 42a-b and 43a-b in moderated to high yields. Interestingly, with allyl hexa-3,5-dienoates 18i-j as the substrate, the rearranged products underwent further aromatization to give uniquely substituted benzyl acids 44a-b.

其次，以含有活泼质子的烯酸炔丙酯18e-k为底物，在DBU为烯醇化碱、TMSCl为硅试剂的条件下，底物18e-h发生了Ireland-Claisen重排/异构化串联反应，得到完全共轭的三烯类化合物42a-b及43a-b；而以己二烯酸炔丙基酯18i-j为底物时，重排/异构化后的产物进一步发生电环化等反应最终得到芳构化产物——取代苯甲酸类化合物44a-b。

We researched on the prepartion of pivotal intermediate 2 and 3 for 1 P-methyl carbapenem antibiotics from intermediate 1, which is subjected to Reformastky reaction, N-alkylation, Dieckmann-type cyclisation, enolization, ester condensation etc. in sequence. The synthesis route of document is optimized by us.

我们研究了1β-甲基碳青霉烯类重要中间体的合成，从中间体1出发经Reformastky反应、水解反应合成出中间体2；经Reformastky反应、烷基化、Dieckmann环合、烯醇化、酯化合成出中间体3，并对其中各步反应作了优化和探索。

We studied DBU-mediated Ireland-Claisen rearrangement. Using DBU as the base for enolization of allylic esters of unsaturated acids 9-16, we found a novel DBU-mediated tandem Ireland-Claisen rearrangement /isomerization reactions and established a consecutive Ireland-Claisen rearrangement /Cope rearrangement.

利用DBU作为烯醇化碱，对含有活泼质子的烯酸烯丙酯类化合物9-16的Ireland-Claisen重排进行了系统的研究，创建了一条新颖的DBU-促进的Ireland-Claisen重排/异构化串联反应及Ireland-Claisen重排/Cope重排的串联反应路线。

Other methyl nucleophiles includingMeMgBr, MeCeCl2, MeTiCl3, Me3Al, Me3ZnMgCl, MeMnClwere tried, but in all these cases no detectable amount of exo-C8-methylated product was obtained. Although protecting C3-carbonyl as 1,3-dioxolanes could be achieved, the serious enolization of C8-carbonyl was still problematic. Converting C9-furan ring to α,β-butenolide did depress the enolization, but desired C8-methylation was completely replaced by migration of the double bond of the butenolide.

在本论文的早期阶段，主要着眼于解决二环[3.2.1]-C8-羰基加成甲基所遇到的C9-呋喃环差向异构化和C3与C8两个羰基之间化学选择性的问题：通过引入不同金属降低甲基试剂的碱性并没有取得甲基化的成功；通过不同的方法将C3-羰基掩蔽，但是C8-羰基的烯醇化依然无法抑制；虽然通过将呋喃环转化为α，β-不饱和-γ-丁内酯可以抑制烯醇化，但内酯环上的双键迁移又成了新的竞争反应。

Finally confirmed that,The thighbone and the osteoporosis morbidity is possibly connected protein 6, respectively are: The lactoferrin light chain, membrane association protein A3, the enolase, ATP gather the enzyme, the acetyl coenzyme A reductases, the myo calcium protein; The lumbar vertebra and the osteoporosis morbidity is possibly connected protein 5, respectively are: The actin, the keratin, the enolase, ATP gather the enzyme, the myosin; The thighbone and the strong bone valuable curative effect is possibly connected protein 9, respectively are: The enolase, ATP gather the enzyme, the myo-calcium protein, the creatine activating enzyme isozyme, the phosphoglyceric acid change flavor the enzyme, the myosin, the lactoferrin light chain, the pyruvic acid activating enzyme isozyme, the crown protein; The lumbar vertebra and the strong bone valuable curative effect are possibly connected protein 8, respectively are: The carbonic anhydrase, the actin, the αB-crystal protein, 3-phospho-glycerol aldehyde oxidase, the serum albumin, ATP gather the enzyme, the myosin, the enolase.

最后确认：股骨与骨质疏松发病可能相关的蛋白6个，分别为：乳铁蛋白轻链、膜联蛋白A3、烯醇化酶、ATP合酶、乙酰辅酶A还原酶、肌钙蛋白；腰椎与骨质疏松发病可能相关的蛋白5个，分别为：肌动蛋白、角蛋白、烯醇化酶、ATP合酶、肌球蛋白；股骨与强骨宝疗效可能相关的蛋白9个，分别为：烯醇化酶、ATP合酶、肌钙蛋白、肌酸激酶同工酶、磷酸甘油酸变味酶、肌球蛋白、乳铁蛋白轻链、丙酮酸激酶同工酶、冠蛋白；腰椎与强骨宝疗效可能相关的蛋白8个，分别为：碳酸酐酶、肌动蛋白、αB-晶体蛋白、3-磷酸甘油醛脱氢酶、血清白蛋白、ATP合酶、肌球蛋白、烯醇化酶。

Breath, muscle contraction of the buttocks; arch body, as far as possible to hold his head, right leg straight towards the ceiling (peg-leg knee in order to avoid muscle tension).

呼气，收缩臀部肌肉；拱起身体，尽量抬起头来，右腿伸直朝向天花板（膝微屈，以避免肌肉紧张）。

The cost of moving grain food products was unchanged from May, but year over year are up 8%.

粮食产品的运输费用与5月份相比没有变化，但却比去年同期高8％。