- TUBULYSIN DERIVATIVES AND METHODS FOR PREPARING THE SAME
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The invention relates to novel means and methods for the synthesis of tubulysin and derivatives thereof, which find their use e.g. as cytotoxic agents in targeted drug delivery. Provided is a method for preparing a tubulysin derivative, comprising reacting compounds A, B and C in a 3- component Passerini reaction, wherein compound A is a carboxylic acid according to the general formula (A); wherein compound B is an aldehyde according to the general formula (B); and wherein compound C is an isocyanide according to the general formula (C).
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Page/Page column 29
(2020/02/16)
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- A short enantioselective total synthesis of (R)- and (S)-pipecolic acid
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A convenient and practical total synthesis of (R)- and (S)-pipecolic acid has been achieved by utilizing chiral cis-aziridine-2-carboxylate as the common synthetic precursor. The synthesis involves regioselective reductive cleavage of the aziridine ring and Wittig olefination as key reactions.
- Chavan, Subhash P.,Khairnar, Lalit B.,Chavan, Prakash N.,Kalbhor, Dinesh B.
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p. 1246 - 1251
(2015/02/19)
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- ANTITHROMBOTIC AGENTS
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This invention relates to L-arginine aldehyde derivatives, having the formula I STR1 where X and Y have the values defined in the description, as well as pharmaceutical formulations containing those compounds and methods of their use as thrombin inhibitor
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- A short enantioselective synthesis of pipecolic acid
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A simple enantioselective route to pipecolic acid is described. The key step involves the Sharpless asymmetric epoxidation of an N-protected aminoheptenol which spontaneously cyclises to a piperidine derivative on deprotection.
- Fernandez-Garcia,McKervey
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p. 2905 - 2906
(2007/10/03)
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- Asymmetric total synthesis of (R)-(-)-cryptopleurine and (R)-(-)-julandine via highly enantioselective amidoalkylations with N-acylhydrazonium salts
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The first enantioselective total syntheses of the phenanthroquinolizidine alkaloid (-)-cryptopleurine (1) and its seco base (-)-julandine [(R)-3] are described. The synthesis of (R)-3 allowed the 9aS configuration to be assigned to natural dextrorotatory julandine as shown by structure (S)-3. Both synthetic approaches are based on the high degree of 1,3-asymmetric induction achieved using an N-acylhydrazonium salt, which belongs to a new structural class of activated azomethines. Upon exposure of methoxylactam 9, with a chiral 2-substituted pyrrolidine auxiliary, to BF3·Et2O and a silyl enol ether the in situ generated N-acylhydrazonium intermediate 10 underwent asymmetric nucleophilic addition to give the (6R)-keto lactams 13 and 14 with complete diastereoselectivity. On the other hand, nucleophilic addition to the N-acylhydrazonium ion 25, with an acyclic chiral auxiliary, showed poor diastereoselectivity. From these results, the high degree of diastereoselection observed for the N-acylhydrazonium ion 10 can be rationalized in terms of the pyramidal stability of the trivalent nitrogen in the chiral pyrrolidine auxiliary. Removal of the chiral auxiliary from 13 and 14 was achieved by reductive N-N bond cleavage using BH3·THF, affording (2S)-piperidine derivatives 15 and 31, respectively, which were transformed into quinolizidinones 30 and 35, respectively, via intramolecular aldol condensation. Reduction of 30 with alane provided (-)julandine [(R)-3]. In addition, 35 was converted to (-)-cryptopleurine (1) in two steps, by radical cyclization with Bu3SnH and AIBN, followed by LiAlH4 reduction.
- Suzuki,Aoyagi,Kibayashi
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p. 6114 - 6122
(2007/10/03)
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- Stereoselective synthesis of (+)-and (-)-lentiginosine
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Simple routes to (1R,2R,8aR)- and (1S,2S,8aS)-lentiginosine have been described, based on Sharpless asymmetric dihydroxylation, starting from (R)- and (S)-pipecolinic acids.
- Gurjar,Ghosh, Lakshmi,Syamala,Jayasree
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p. 8871 - 8872
(2007/10/02)
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- An Asymmetric Synthesis of 2-Substituted Piperidines through Ozonolysis of Cyclopentenes and Reductive Aminocyclization
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By the action of ozone, sodium cyanoborohydride and the optically active benzylic amines 2, the 1-substituted cyclopentenes 1, 5 and 9 were converted to a diastereometric mixture of 1,2-disubstituted piperidines (3, 6 and 10), respectively.Hydrogenation of these compounds and the following work-up yielded optically active 2-alkylpiperidines (4, up to 68percente.e.), pipecolic acid (7, 84percent e.e.) and 2-(hydroxymethyl)piperidine (11, up to 85percente.e.).Chromatographic separation of the major isomers of 3b and 6 enabled optically pure coniine (4b) and pipecolic acid (7) to be prepared, respectively.
- Kawaguchi, Mamoru,Hayashi, Osamu,Sakai, Noriyuki,Hamada, Masayuki,Yamamoto, Yukio,Oda, Jun'ichi
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p. 3107 - 3112
(2007/10/02)
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- A New Class of Chiral Smectic Liquid Crystals: Substituted Biphenylylcyclohexylideneethanones Having an Axial Chirality
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The introduction of chiral cyclohexylideneethanone unit in a potential mesomorphic structure leads to the first family of optically active liquid crystals having an axial chirality.Racemic compounds 2 were synthesized by a Wittig-type coupling between β-keto phosphonates 6 (R1 = n-C5H11) and substituted cyclohexanone 7 (R2 = H, CH3, t-Bu, OCH3, O-n-C5H11, CO2Et, OCOC6H4CN, OCOC6H4Cl).The optically active molecules 12 were prepared by a new route using the asymmetric coupling of a carbanion α to a chiral sulfoxide 9 (R2 = n-C5H11, CH2OEt) and a substituted biphenyl acid chloride (Ar = R'C6H4C6H4 with R' = n-C5H11, CH3O, n-C8H17O, CN) followed by a stereospecific pyrolytic elimination of the sulfoxide moiety.Derivatives containing only one aromatic ring were not mesomorphic in contrast to those having a biphenyl system.
- Solladie, Guy,Zimmermann, Richard
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p. 4062 - 4068
(2007/10/02)
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