马蔺子乙素的合成

以3-甲氧基水杨醛为原料,经羟基保护、缩合、还原,脱保护基和催化氧化五步反应合成马蔺子乙素。     

检查点激酶Bub1抑制剂2OH-BNPP1的合成研究

目的：研究检查点激酶Bub1抑制剂2OH-BNPP1的合成方法。方法：将2-羟基苯乙酸转化成苄基保护的酰氯,再与丙二腈缩合得化合物5,经硫酸二甲酯对5的烯醇式甲基化得化合物6,6与叔丁基肼反应完成了吡唑环的构筑以形成化合物7,7与甲酰胺作用构筑并嘧啶环,最后将所得的化合物8脱苄,即得目标物1。结果与结论：以苄基保护起始原料的2-位酚羟基,使路线中的各步中间体稳定、极性小而易于硅胶柱色谱分离,最后催化脱苄几乎定量完成,保证了终产物的化学纯度。目标物的HPLC检测纯度为98.8 %,其结构经ESI&;#61485;MS和1H&;#61485;NMR确证。     

硫酸特布他林的合成

以３,５－二羟基苯甲酸为起始原料,经酯化,苄基保护,水解,酰化,氧化,缩合、还原,脱苄制成硫酸特布他林,总收率２１％。     

氢溴酸达非那新的合成

反式-4-羟基-L-脯氨酸经脱羧、N-保护、Mitsunobu反应、缩合、脱保护基、水解、与L-（＋）-酒石酸成盐及碱化等8步反应制得3-（曲-（-）-（1-氨甲酰基-1，1-二苯基甲基）四氢吡咯，然后与5-（2-溴乙基）-2,3-二氢苯并呋喃缩合、成盐制得氢溴酸达非那新，总收率约为2％。     

消旋藁本酚及其类似物的合成研究

藁本酚是从中药藁本根茎中分离到的新的倍半萜类化合物,有较强的免疫抑制、抗炎活性。为了进一步研究该化合物的药理活性,对其进行了合成研究。以异丁醛、间甲酚为起始原料,经溴取代、芳烃碘代、羟基保护、格氏反应、Aldol缩合反应,脱保护等6步反应完成了消旋藁本酚的全合成。经¹H-NMR,MS,IR分析,并与天然产物藁本酚比较,目的物得到证实。为了研究藁本酚的构效关系,设计并合成了5个类似物。初步的药理研究没有发现相应的生理活性。     

HIV蛋白酶抑制剂利托那韦的合成工艺改进

目的改进HIV蛋白酶抑制剂利托那韦的合成工艺。方法以L-苯丙氨酸为原料,经三苄基保护、还原性缩合及格氏试剂偶联、α,β-不饱和酮还原、Boc保护、选择性脱苄基、缩合、脱Boc基、再次缩合得到利托那韦。结果与结论目标化合物的结构经~1H-NMR、~(13)C-NMR和MS谱确证,总收率为73.3%(以L-苯丙氨酸计),HPLC法测定纯度达99.8%。与文献报道的工艺相比,该路线操作简易、成品质量好、生产成本较低,有利于工业化生产。     

3-羟基-6-O-甲基红霉素-9-肟基衍生物的合成及体外抗菌活性

目的　寻找并合成抗耐药菌活性的 3位羟基红霉素衍生物。方法　以红霉素A为原料 ,经 9位酮基肟化 ,9位肟羟基 ,2′位羟基和 3′位二甲胺基同时苄基化 ,6位羟基甲基化 ,水解去 3位克拉定糖 ,氢化还原脱苄基 ,对甲基苄基或邻氯苄基取代 9位肟羟基等 6步反应 ,制得 3 羟基 6 O 甲基红霉素 9 肟基衍生物 ,其结构经1 3 CNMR ,FAB MS确证。结果　共制得 7个化合物 ,对其中 4个 (5 - 8)未见报道的化合物进行了体外抗菌活性测定。结论　 5 ,7,8对部分红霉素诱导耐药菌有一定的活性     

丹参素结构中醇羟基的修饰与初步活性评价

目的设计合成系列在丹参素醇羟基部位修饰的新衍生物,初步探索醇羟基在丹参素生物活性中的作用。方法丹参素的酚羟基以及羧基经苄基保护后,其醇羟基与相应的基团在不同的催化剂下缩合生成醚键以及酯键化合物,然后脱除保护基得到醇羟基修饰的衍生物。通过体外的心肌细胞氧化损伤模型初步评价新衍生物的生物活性,分析其构效关系。结果合成了11个丹参素新衍生物,并进行了结构确证;活性实验显示,醇羟基上醚键与酯键修饰的衍生物活性均没有明显高于母药丹参素。结论裸露的醇羟基可能是丹参素发挥作用的必需基团。     

克拉屈滨的合成

2-脱氧核糖经甲基化、羟基保护和氯代反应得到1-氯-2-脱氧-3,5-二-O-对甲苯甲酰基-α-D-顺-呋喃核糖,与2-氯-6-氨基嘌呤缩合后脱保护即可制得抗白血病药克拉屈滨,总收率21%.     

L-核糖的合成

L-阿拉伯糖依次经苄基和亚异丙基保护羟基得1-O-苄基-3,4-O-亚异内基-β-L-阿拉伯糖,续经TEMPO/NaOCl/KBr氧化、硼氢化钠还原、80%乙酸脱亚异丙基保护得1-O-苄基-β-L吡喃核糖,最后经催化氢解脱苄制得L-核糖,总收率约61%.     

4，4’-二羟基二苯甲酮的合成

用乙酸酐保护对羟基苯甲酸的羟基,再经氯化亚砜酰氯化、与苯酚成酯得到对乙酰氧基苯甲酸苯酯,最后经脱乙酰保护基和Fries重排得到4,4'-二羟基二苯甲酮,总收率68%。     

拉尼那米韦辛酯的合成工艺研究(英文)

目的研究抗流感药物拉尼那米韦辛酯的合成工艺。方法以N-乙酰神经氨酸作为起始原料,经过酯化、酰化、成环、脱保护、保护、叠氮化、甲基化及水解等13步反应制备拉尼那米韦辛酯。结果与结论经过对合成工艺的改进得到了目标产物,其结构经1H-NMR、13C-NMR、LC-MS和HR-MS予以确证,总收率为16%。     

Improved selectivity in the removal of the tert.-butyloxycarbonyl group

Removal of the tert.-butyloxycarbonyl group by trifluoroacetic acid in the presence of benzyloxycarbonyl groups, benzyl esters and benzyl ethers is rendered more selective by dilution with acetic acid. Trifluoroacetic acid-acetic acid mixtures, however, cause acetylation of hydroxyl groups and also some formation of tert.-butyl esters at free carboxyls. Hence, such mixtures are useful only for the deprotection of intermediates in which the hydroxyl and carboxyl groups are fully blocked. A search for a diluent without such inherent limitation led to the application of a mixture of phenol and p-cresol. Dilution of trifluoroacetic acid with phenols both improved the selectivity in the removal of the tert.-butyloxycarbonyl group and suppressed the alkylation of amino acid side chains as well. A 4:3:3 mixture of trifluoroacetic acid, phenol and p-cresol was found useful in the practical execution of partial deprotection.     

Mode of action of butylated hydroxyanisole (BHA) and other phenols in preventing loss of 11 beta-hydroxylase activity in cultured bovine adrenocortical cells

When cultured bovine adrenocortical cells are incubated with cortisol, or other steroids that are pseudosubstrates for 11 beta-hydroxylase (cytochrome P-45011 beta), the activity of the enzyme decreases. In previous experiments, three substances were shown to protect 11 beta-hydroxylase against loss of enzymatic activity in the presence of pseudosubstrates:BHA (butylated hydroxyanisole,2(3)-tert-butyl-4-methoxyphenol), dimethyl sulfoxide (DMSO), and metyrapone. The present experiments examine the protective effects of several phenolic analogs of BHA in this system, and compare their activities to that of DMSO and metyrapone. When a variety of analogs of BHA were tested for their abilities to prevent loss of 11 beta-hydroxylase activity in cultured adrenocortical cells incubated with 50 microM cortisol for 24 hr, phenol itself was found to be about equipotent with BHA. Addition of methyl, methoxy and benzyl groups to phenol did not diminish protective activity of the compound, but addition of one and particularly two tert-butyl groups greatly diminished activity. Thus, BHT(2,6-di-t-butyl-4-methylphenol) was inactive, in contrast to BHA. The hydroxy group of phenol was essential since benzene and fluorobenzene were inactive. Compounds with multiple hydroxyl groups were not as active as phenol itself, with the exception of catechol. No products of phenol formed during incubations of cells with cortisol were detected by high performance liquid chromatography. Estimated EC50 values for protection of 11 beta-hydroxylase by phenols were about 100 microM, whereas the EC50 values for dimethyl sulfoxide and metyrapone were 10 mM and 300 nM respectively. On a semilogarithmic plot, the dose-response curves for all these compounds were approximately parallel. To aid in determining the mechanism of protection of 11 beta-hydroxylase, phenols and DMSO were tested for prevention of loss of 11 beta-hydroxylase activity at three different oxygen concentrations (2, 5, and 19% O2). Lowering the oxygen concentration itself resulted in a small diminution of the loss of 11 beta-hydroxylase. Phenols and dimethyl sulfoxide were more effective at low oxygen and less effective in air. Because the cytochrome P-450 inhibitor metyrapone was found previously to be very effective in protecting 11 beta-hydroxylase against loss of activity, we examined whether phenols and dimethyl sulfoxide may act by directly inhibiting 11 beta-hydroxylase activity. In a 1-hr incubation with cells, BHA, phenol, and dimethyl sulfoxide all inhibited 11 beta-hydroxylase, but at concentrations that ranged from 4- to greater than 100-fold higher than those required for protection.(ABSTRACT TRUNCATED AT 400 WORDS)     

Alkenylidene bisphenols, a new class of bisphenol bactericide.

Alkenylidene bisphenols are prepared by condensation of an appropriate phenol with a haloacetaldehyde, followed by base-induced elimination, or by condensation of the corresponding aryl methyl ether, elimination, and deprotection of the phenol with boron tribromide. The resulting compounds may be further elaborated by reactions on the aromatic nucleus. A series of 13 such compounds showed activity against Staphylococcus aureus; the most active was 1,1-dichloro-2-(3-allyl-5-chloro-2-hydroxphenyl)-2-(5-chloro-2-hydroxyphenyl)ethylene (16), MIC 0.16 microgram/mL. 1,1-Dichloro-2,2-bis(5-chloro-2-hydroxyphenyl)ethylene (6) was similar in its activity and spectrum to hexachlorophene.     

一种β，γ-不饱和醛的合成及其光化学反应研究

目的设计合成β,γ-不饱和醛,并研究其光化学反应机制,为天然产物及其中间体的光化学合成提供新的参考。方法以异丁醛为原料,经缩合、醛基保护、氧化、Wittig反应、脱水、脱保护基6步反应制得目标化合物。用高压汞灯照射目标化合物后所得产物与β,γ-不饱和甲基酮进行比较分析。结果目标化合物的结构经高分辨质谱、核磁共振谱确证。目标化合物经光照后发生NorrishI型裂解反应,与β,γ-不饱和甲基酮相比,没有发生ODPM重排反应。结论甲基对β,γ-不饱和酮（醛）的光化学反应行为有一定的影响。     

克拉霉素的合成

红霉素碱经肟化、保护再经甲基化、脱保护得到克拉霉素 ,总收率达 40 %以上。     

Incomplete trifluoroacetic acid deprotection of asparagine-trityl-protecting group in the vicinity of a reduced peptide bond

: During the Fmoc solid-phase synthesis of reduced peptide bond analogues, we observed that the trityl protection of an asparagine residue in the vicinity of a reduced peptide bond is not cleaved completely after the final trifluoroacetic acid deprotection step. The relative position of the Asn side-chain amine and of the aminomethylene bond as well as the preferential protonation of the secondary amine can be used to explain this phenomenon. We show that longer deprotection times or the use of methyl-trityl protection partially improves the yield of the Asn-deprotected peptide whereas xanthenyl protection totally overcomes this problem.     

9-肟基-3-酮基-6-O-甲基红霉素的合成

以红霉素为原料，经肟化、苄基化、甲基化、水解、氧化和氢化还原等6步反应，制得9-肟基-3-酮基-6-O-甲基红霉素。总收率41％。