- A convenient synthesis of (1S)-tert-butyl-1,2-ethylenediamine
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A practical four-step synthesis of (1S)-tert-butyl-1,2-ethylenediamine has been developed. The sequence proceeds in good overall yield via crystalline intermediates and provides the title compound in 99.3% ee. Copyright (C) 2000 Elsevier Science Ltd.
- Busacca, Carl A.,Grossbach, Danja,Spinelli, Earl
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- 2-(1H-INDOLE-3-CARBONYL)-THIAZOLE-4-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ARYL HYDROCARBON RECEPTOR (AHR) AGONISTS FOR THE TREATMENT OF E.G. ANGIOGENESIS IMPLICATED OR INFLAMMATORY DISORDERS
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2-(1H-lndole-3-carbonyl)-thiazole-4-carboxamide derivatives and the corresponding imidazole, oxazole and thiophene derivatives and related compounds as aryl hydrocarbon receptor (AHR) agonists for the treatment of angiogenesis implicated disorders, such as e.g. retinopathy, psoriasis, rheumatoid arthritis, obesity and cancer, or inflammatory disorders. The present description discloses the synthesis and characterisation of exemplary compounds as well as pharmacological data thereof (e.g. pages 27 to 32 and 59 to 219; examples 1 to 8; compounds 1-1 to 1-97; tables 1-a, 2 and 3).
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Paragraph 00162; 00320
(2021/06/26)
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- N-1 BRANCHED ALKYL ETHER SUBSTITUTED IMIDAZO[4,5-C]QUINOLINE COMPOUNDS, COMPOSITIONS, AND METHODS
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Imidazo[4,5-c]quinoline compounds having a substituent that is attached at the N-1 position by a branched group, single enantiomers of the compounds, pharmaceutical compositions containing the compounds, and methods of making the compounds are disclosed. Methods of use of the compounds as immune response modifiers, for inducing cytokine biosynthesis in humans and animals, and in the treatment of diseases including infectious and neoplastic diseases are also disclosed.
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- N-1 BRANCHED ALKYL SUBSTITUTED IMIDAZO[4,5-C]QUINOLINE COMPOUNDS, COMPOSITIONS, AND METHODS
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Imidazo[4,5-c]quinoline compounds having a substituent that is attached at the N-1 position by a branched group, single enantiomers of the compounds, pharmaceutical compositions containing the compounds, and methods of making the compounds are disclosed. Methods of use of the compounds as immune response modifiers, for inducing (or inhibiting) cytokine biosynthesis in humans and animals, and in the treatment of diseases including infectious and neoplastic diseases are also disclosed.
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- Isoselective ring-opening polymerization and asymmetric kinetic resolution polymerization of: Rac -lactide catalyzed by bifunctional iminophosphorane-thiourea/urea catalysts
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A series of iminophosphorane-thiourea/urea bifunctional catalysts was synthesized and utilized for the isoselective ring-opening polymerization of rac-lactide. The ROPs were promoted efficiently, affording the polylactides with controlled molecular weight, narrow molecular weight distribution and well-defined end groups without undesired side reactions. The experiment data revealed that ROPs of rac-LA are a "controlled/living" process. The highest stereoselectivity (Pm) was up to 0.80 using rac-IPU-1 under mild reaction conditions. The mechanistic study indicated that stereoselective ROPs of rac-LA were mainly controlled by a chain-end control mechanism when using rac/(R,R)-IPTU-1/IPU-1 as catalysts. Additionally, the ee values of -11% at 0 °C and -17% at -40 °C were achieved at about 50% conversion using (S)-IPU-2 as a chiral catalyst. The selectivity factor (s = kL/kD) of 1.6 indicated that a clear kinetic resolution occurred and the enantiomorphic site control mechanism was involved.
- Lv, Chengdong,Zhou, Li,Yuan, Ruiting,Mahmood, Qaiser,Xu, Guangqiang,Wang, Qinggang
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supporting information
p. 1648 - 1655
(2020/02/04)
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- Asymmetric kinetic resolution of sulfides for the construction of unsymmetric sulfides and chiral 3,3-disubstituted oxindoles
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A range of 3,3-disubstituted oxindoles accessed using para-quinone methides derived from isatins with thiols were used for the formation of unsymmetrical disulfides, and 3,3-disubstituted oxindoles with a chiral quaternary carbon center and unsymmetric di
- Wang, Kaiye,Xiang, Yanan,Shi, Zhujun,Wang, Hongyu,Li, Na,Tang, Bo
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supporting information
p. 6351 - 6354
(2019/07/10)
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- Preparation method of N-alkoxy or benzyloxycarbonyl chiral amino acid
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The invention provides a preparation method of N-alkoxy or benzyloxycarbonyl amino acid, particularly provides a preparation method of N-alkoxy or benzyloxycarbonyl chiral amino acid, and more particularly provides a preparation method of N-alkoxy or benzyloxycarbonyl-L-amino acid or N-alkoxy or benzyloxycarbonyl-D-amino acid. In the preparation method, a resolving agent is not required for chemical resolution, and the N-alkoxy or benzyloxycarbonyl chiral amino acid with high optical purity can be prepared. The N-alkoxy or benzyloxycarbonyl chiral amino acid is a very important medicine intermediate. According to the preparation method of the N-alkoxy or benzyloxycarbonyl-L-amino acid, provided by the invention, a reaction formula is as follows in the description, wherein R1 is an alkyl group, preferably a tert-butyl group; R2 is an azido group or an imide group, n is 0 or 1, and m is 1.
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- Chemo- and Diastereoselective N-Heterocyclic Carbene-Catalyzed Cross-Benzoin Reactions Using N-Boc-α-amino Aldehydes
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N-Boc-α-amino aldehydes are shown to be excellent partners in cross-benzoin reactions with aliphatic or heteroaromatic aldehydes. The chemoselectivity of the reaction and the facial selectivity on the amino aldehyde allow cross-benzoin products to be obtained in good yields and good diastereomeric ratios. The developed method is utilized as the key step in a concise total synthesis of d-arabino-phytosphingosine.
- Haghshenas, Pouyan,Gravel, Michel
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supporting information
p. 4518 - 4521
(2016/09/28)
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- Tunable Bifunctional Phosphine-Squaramide Promoted Morita-Baylis-Hillman Reaction of N-Alkyl Isatins with Acrylates
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A series of highly tunable bifunctional phosphine-squaramide H-bond donor organocatalysts 6 has been synthesized from inexpensive and commercially available β-amino alcohols in moderate yields. Catalyst 6 can efficiently promote the asymmetric Morita-Baylis-Hillman (MBH) reaction of N-alkyl isatins with acrylate esters providing the chiral 3-substituted 3-hydroxy-2-oxindoles in good yields and enantioselectivities (up to 93 yield and 95 ee), in which the challenging substrate tert-butyl acrylate 9d, provided the best ee value to date. Moreover, this methodology was applied successfully in the synthesis of chiral cyclic spiropyrrolizidineoxindole and γ-butyrolactone derivatives without enantioselectivity deterioration. The possible mechanism of this MBH reaction was also investigated by 31PNMR, ESI-MS and KIE studies. The KIE experiments show that the electrophilic addition of N-methyl isatin to the complex of acrylate ester and phophine-squaramide is the rate-determing step of the asymmetric MBH reaction.
- Dong, Ze,Yan, Chao,Gao, Yongzhi,Dong, Chune,Qiu, Guofu,Zhou, Hai-Bing
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p. 2132 - 2142
(2015/06/23)
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- Asymmetric Multicomponent Sulfa-Michael/Mannich Cascade Reaction: Synthetic Access to 1,2-Diamino-3-Organosulfur Compounds and 2-Nitro Allylic Amines
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A novel catalytic asymmetric three-component intermolecular sulfa-Michael/Mannich cascade reaction has been developed using a chiral multifunctional catalyst. This reaction provides facile access to 1-amino-2-nitro-3-organosulfur compounds bearing three c
- Hou, Wenduan,Wei, Qi,Liu, Guisheng,Chen, Jing,Guo, Jing,Peng, Yungui
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supporting information
p. 4870 - 4873
(2015/10/12)
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- Copper(I)/ABNO-catalyzed aerobic alcohol oxidation: Alleviating steric and electronic constraints of Cu/TEMPO catalyst systems
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Cu/TEMPO catalyst systems promote efficient aerobic oxidation of sterically unhindered primary alcohols and electronically activated substrates, but they show reduced reactivity with aliphatic and secondary alcohols. Here, we report a catalyst system, consisting of (MeObpy)CuI(OTf) and ABNO (MeObpy =4,4′-dimethoxy-2,2′-bipyridine; ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl), that mediates aerobic oxidation of all classes of alcohols, including primary and secondary allylic, benzylic, and aliphatic alcohols with nearly equal efficiency. The catalyst exhibits broad functional group compatibility, and most reactions are complete within 1 h at room temperature using ambient air as the source of oxidant.
- Steves, Janelle E.,Stahl, Shannon S.
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supporting information
p. 15742 - 15745
(2013/11/06)
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- Synthesis of chiral aminophosphines from chiral aminoalcohols via cyclic sulfamidates
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(Chemical Equation Presented) Protic aminophosphines with multiple chiral centers were synthesized in good yields and high purity by the nucleophilic ring-opening of N-protected cyclic sulfamidates with metal phosphides, followed by hydrolysis and deprote
- Guo, Rongwei,Lu, Shuiming,Chen, Xuanhua,Tsang, Chi-Wing,Jia, Wenli,Sui-Seng, Christine,Amoroso, Dino,Abdur-Rashid, Kamaluddin
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supporting information; experimental part
p. 937 - 940
(2010/05/02)
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- Discovery of novel P3 sulfonamide-capped inhibitors of HCV NS3 protease. Inhibitors with improved cellular potencies
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Hepatitis C Virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 200 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-α or PEG-interferon alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only ~50% of the patients showing sustained virological response. We recently disclosed the discovery of Boceprevir, SCH 503034 (1), which is a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been shown to be efficacious in humans and is currently undergoing clinical trials. As second generation compounds, we have further explored various novel structures with the aim of improving enzyme and cellular binding activities of 1. Herein, we disclose our efforts toward the identification of a novel P3 sulfonamide-capped inhibitor that demonstrated improved binding and cellular activity compared to 1. X-ray structure of one of these inhibitors bound to the enzyme revealed a hydrogen bond of the P3 sulfonamide group to Cys-159 which resulted in improved binding and cellular potency.
- Venkatraman, Srikanth,Blackman, Mellissa,Wu, Wanli,Nair, Latha,Arasappan, Ashok,Padilla, Angela,Bogen, Stéphane,Bennett, Frank,Chen, Kevin,Pichardo, John,Tong, Xiao,Prongay, Andrew,Cheng, Kuo-Chi,Girijavallabhan, Viyyoor,George Njoroge
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experimental part
p. 4486 - 4495
(2009/10/10)
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- Novel potent inhibitors of hepatitis C virus (HCV) NS3 protease with cyclic sulfonyl P3 cappings
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Extensive SAR studies of the P3 capping group led to the discovery of a series of potent inhibitors with sultam and cyclic sulfonyl urea moieties as the P3 capping. The bicyclic thiophene-sultam or phenyl-sultam cappings were selected for further SAR development. Modification at the P3 side chain determined that the tert-butyl group was the best choice at that position. Optimization of P1 residue significantly improved potency and selectivity. The combination of optimal moieties at all positions led to the discovery of compound 33. This compound had the best overall profile in potency and PK profile: excellent Ki* of 5.3 nM and activity in replicon (EC90) of 80 nM, extremely high selectivity of 6100, and a good rat PO AUC of 1.43 μM h.
- Chen, Kevin X.,Vibulbhan, Bancha,Yang, Weiying,Nair, Latha G.,Tong, Xiao,Cheng, Kuo-Chi,Njoroge, F. George
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body text
p. 1105 - 1109
(2009/08/07)
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- Molecular iodine-catalyzed facile procedure for N-Boc protection of amines
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An efficient and practical protocol for the protection of various structurally and electronically divergent aryl and aliphatic amines using (Boc)2O in the presence of a catalytic amount of molecular iodine (10 mol%) under solvent-free conditions at ambient temperature is presented.
- Varala, Ravi,Nuvula, Sreelatha,Adapa, Srinivas R.
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p. 8283 - 8286
(2007/10/03)
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- 3,4-(cyclopentyl)-fused proline compounds as inhibitors of hepatitis C virus NS3 serine protease
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The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.
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Page/Page column 123
(2008/06/13)
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- Nucleophilic acyl substitutions of anhydrides with protic nucleophiles catalyzed by amphoteric, oxomolybdenum species
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(Chemical Equation Presented) Among six different group VIb oxometallic species examined, dioxomolybdenum dichloride and oxomolybdenum tetrachloride were the most efficient catalysts to facilitate nucleophilic acyl substitution (NAS) of anhydrides with a myriad array of alcohols, amines, and thiols in high yields and high chemoselectivity. In contrast to the well-recognized redox chemical behaviors associated with oxomolybdenum(VI) species, the catalytic NAS was unprecedented and tolerates virtually all kinds of functional groups. By using benzoic anhydride as a mediator for in situ generation of an incipient mixed anhydride-MoO2Cl2 adduct with a given functional alkanoic acid, one can achieve oleate, dipeptide, diphenylmethyl, N-Fmoc-α-amino, pyruvic, and tert-butylthio ester, N-tert-butylamide, and trityl methacrylate syntheses with appropriate protic nucleophiles. The amphoteric character of the Mo=O unit in oxomolybdenum chlorides was found to be responsible for the catalytic NAS profile as supported by a control NAS reaction of using an authentic adduct-MoOCl2(O2-CBu t)2 between pivalic anhydride and MoO2Cl 2 as the catalyst.
- Chen, Chien-Tien,Kuo, Jen-Huang,Pawar, Vijay D.,Munot, Yogesh S.,Weng, Shieu-Shien,Ku, Cheng-Hsiu,Liu, Cheng-Yuan
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p. 1188 - 1197
(2007/10/03)
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- Exploration of the P1 SAR of aldehyde cathepsin K inhibitors.
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The synthesis and biological activity of a series of aldehyde inhibitors of cathepsin K are reported. Exploration of the properties of the S(1) subsite with a series of alpha-amino aldehyde derivatives substituted at the P(1) position afforded compounds with cathepsin K IC(50)s between 52 microM and 15 nM.
- Catalano, John G,Deaton, David N,Furfine, Eric S,Hassell, Annie M,McFadyen, Robert B,Miller, Aaron B,Miller, Larry R,Shewchuk, Lisa M,Willard Jr., Derril H,Wright, Lois L
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p. 275 - 278
(2007/10/03)
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- Stereodivergent synthesis of chiral 2-alkenylaziridines: Palladium(0)-catalyzed 2,3-cis-selective aziridination and base-mediated 2,3-trans-selective aziridination
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Whereas treatment of the allylic mesylates of N-protected 2-alkyl-4-amino-(E)-2-alken-1-ols with sodium hydride in DMF yields exclusively the corresponding thermodynamically less stable 2,3-trans-2-alkenyl-3- alkylaziridines, exposure of the methyl carbon
- Ohno, Hiroaki,Takemoto, Yoshiji,Fujii, Nobutaka,Tanaka, Tetsuaki,Ibukab, Toshiro
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p. 111 - 119
(2007/10/03)
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- Versatile synthons for optically pure alpha-amino aldehydes and alpha-amino acids: (+)- and (-)-4,5-dialkoxy-2-oxazolidinones.
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Both enantiomers of trans-5-benzyloxy-4-methoxy- (BMOx) and trans-4,5-dimethoxy-2-oxazolidinones (DMOx), which are readily accessible from simple 2-oxazolone heterocycles, represent good candidates for a new class of chiral synthons for use in the preparation of optically pure alpha-amino aldehydes and alpha-amino acids, respectively.
- Morita,Nagasawa,Yahiro,Matsunaga,Kunieda
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p. 897 - 899
(2007/10/03)
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- Versatile chiral bidentate ligands derived from α-amino acids: Synthetic applications and mechanistic considerations in the palladium- mediated asymmetric allylic substitutions
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A new class of chiral amidine-phosphine hybrid ligands 7a,b, which are readily accessible from the corresponding α-amino acids, were developed. A versatility for construction of new ligands is desirable, by which a variety of reactions and substrates become applicable. Indeed, a variety of modifications, such as exchange reactions to other amino groups in the amidine skeleton and the production of other types of ligands, are possible using the precursor compounds of 7a. Thus, novel chiral ligands 7c,d, 8, 11, and 13, which provide sterically and electronically different chiral circumstances, were prepared and used for the palladium-mediated asymmetric allylic substitutions of both acyclic and cyclic compounds. In these reactions, high levels of asymmetric induction were achieved for both substrates. A marked advancement of reactivity and enantioselectivity in palladium-catalyzed asymmetric allylations of 1,3-diphenylpropen-2-yl pivalate 14a was attained by examination of electronic substituent effects in a new series of chiral P-N and S-N hybrid ligands 8 and 11. Mechanistic views concerning the enantiodiscriminating step were demonstrated, in which a good correlation between a novel Pr/Mr concept and the absolute configuration of allylation products are discussed for the prediction of enantioselecting direction. The use of ketene silyl acetals as nucleophiles was investigated and compared with the corresponding harder anionic carbon nucleophiles. The former nucleophiles afforded higher enantioselectivity in asymmetric allylic transformations of 14a.
- Saitoh, Akihito,Achiwa, Kazuo,Tanaka, Kiyoshi,Morimoto, Toshiaki
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p. 4227 - 4240
(2007/10/03)
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- Asymmetric syntheses of (R)- and (S)-2-aminobutanesulfonic acid and their 3,3-dimethylderivatives
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(R)- and (S)-2-aminobutanesulfonic acid, 3a and 3b, and (R)- and (S)-2-amino-3,3-dimethylbutanesulfonic acid, 4a and 4b, were synthesized from the corresponding N-Boc protected β-amino alcohols in good yields and high enantiomeric purities (> 99% ee).
- Braghiroli, Daniela,Di Bella, Maria
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p. 2145 - 2150
(2007/10/03)
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- Novel cytotoxic 3'-(tert-butyl) 3'-dephenyl analogs of paclitaxel and docetaxel
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3'-(tert-Butyl) 3'-dephenyl analogs of paclitaxel were synthesized from 10-deacetylbaccatin III and oxazolidinecarboxylic acid 7 followed by acylation of intermediate amines 10 and 11. Oxazolidinecarboxylic acid 7 was prepared in five steps and in good ov
- Ali,Hoemann,Aube,Mitacher,Georg,McCall,Jayasinghe
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p. 3821 - 3828
(2007/10/03)
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