- Stereoselective Total Synthesis of Carolacton
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A short and convergent strategy for the stereoselective total synthesis of biologically active natural product carolacton has been accomplished. Our synthesis highlights the Urpi acetal aldol, Crimmins aldol, Ireland-Claisen rearrangement, TiCl4/sub
- Kuilya, Tapan Kumar,Goswami, Rajib Kumar
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- 3,6-DIAMINO-PYRIDAZIN-3-YL DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR USES AS PRO-APOPTOTIC AGENTS
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Compounds of formula (I) wherein Het1, Het2, R1, R2 and R3 are as defined in the description. Medicaments.
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- Asymmetric Total Synthesis of Mycobacterial Diacyl Trehaloses Demonstrates a Role for Lipid Structure in Immunogenicity
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The first asymmetric total synthesis of three structures proposed for mycobacterial diacyl trehaloses, DAT1, DAT2, and DAT3 is reported. The presence of two of these glycolipids, DAT1 and DAT3, within different strains of pathogenic M. tuberculosis was co
- Holzheimer, Mira,Reijneveld, Josephine F.,Ramnarine, Alexandrea K.,Misiakos, Georgios,Young, David C.,Ishikawa, Eri,Cheng, Tan-Yun,Yamasaki, Sho,Moody, D. Branch,Van Rhijn, Ildiko,Minnaard, Adriaan J.
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p. 1835 - 1841
(2020/08/26)
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- Homo-Roche ester derivatives by asymmetric hydrogenation and organocatalysis
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Asymmetric hydrogenation routes to homologues of The Roche ester tend to be restricted to hydrogenations of itaconic acid derivatives, that is, substrates that contain a relatively unhindered, 1,1-disubstituted alkene. This is because in hydrogenations mediated by RhP2 complexes, the typical catalysts, it is difficult to obtain high conversions using the alternative substrate for the same product, the isomeric trisubstituted alkenes (D in the text). However, chemoselective modification of the identical functional groups in itaconic acid derivatives are difficult; hence, it would be favorable to use the trisubstituted alkene. Trisubstituted alkene substrates can be hydrogenated with high conversions using chiral analogs of Crabtree's catalyst of the type IrN(carbene). This paper demonstrates that such reactions are scalable (tens of grams) and can be manipulated to give optically pure homo-Roche ester chirons. Organocatalytic fluorination, chlorination, and amination of the homo-Roche building blocks was performed to demonstrate that they could easily be transformed into functionalized materials with two chiral centers and α,ω-groups that provide extensive scope for modifications. A synthesis of (S,S)- and (R,S)-γ-hydroxyvaline was performed to illustrate one application of the amination product.
- Khumsubdee, Sakunchai,Zhou, Hua,Burgess, Kevin
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p. 11948 - 11955
(2014/01/06)
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- Synthesis of stereopure acyclic 1,5-dimethylalkane chirons: Building blocks of highly methyl-branched natural products
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An efficient synthetic method towards stereopure acyclic 1,5-dimethylalkane building blocks from methyl (2R)-3-hydroxy-2-methylpropionate (R)-1 (>99% ee) and methyl (2S)-3-hydroxy-2-methylpropionate (S)-1 (>99% ee) through a series of chemical transformat
- Li, Nan-Sheng,Piccirilli, Joseph A.
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p. 9633 - 9641
(2013/10/22)
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- A concise asymmetric synthesis of (-)-rasfonin
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A very efficient total synthesis of the apoptosis inducer (-)-rasfonin has been developed using CuBr/JosiPhos catalyzed iterative asymmetric conjugate addition of MeMgBr and Feringa's butenolide.
- Huang, Yange,Minnaard, Adriaan J.,Feringa, Ben L.
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- Catalytic asymmetric synthesis of mycolipenic and mycolipanolic acid
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The first asymmetric synthesis of mycolipenic acid and mycolipanolic acid by using an improved iterative procedure involving catalytic asymmetric conjugate addition of MeMgBr as the key step is described. Mycolipenic and mycolipanolic acid are obtained in 11 steps with perfect stereocontrol, and both acids are identical to their counterparts from natural sources.
- Horst, Bjorn Ter,Van Wermeskerken, Jeroen,Feringa, Ben L.,Minnaard, Adriaan J.
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supporting information; experimental part
p. 38 - 41
(2010/03/24)
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- Formal synthesis of the anti-angiogenic polyketide (-)-borrelidin under asymmetric catalytic control
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Borrelidin (1) is a polyketide that possesses extremely potent antiangiogenesis activity. This paper describes its formal total synthesis by the most efficient route to date. This modular approach takes optimal benefit of asymmetric catalysis and permits the synthesis of analogues; in addition, the high yields and selectivities obtained eliminate the need for separation of stereoisomers. The upper half of borrelidin has been accessed by iterative copper-catalysed asymmetric conjugate addition of methylmagnesium bromide, whereas synthesis of the lower half of the molecule was achieved by relying on asymmetric hydrogenation and cross-methathesis as key steps.
- Madduri, Ashoka V. R.,Minnaard, Adriaan J.
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supporting information; experimental part
p. 11726 - 11731
(2010/11/18)
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- Anti-AIDS agents 81. design, synthesis, and structure-activity relationship study of betulinic acid and moronic acid derivatives as potent HIV maturation inhibitors
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In our continuing study of triterpene derivatives as potent anti-HIV agents, different C-3 conformationally restricted betulinic acid (BA, 1) derivatives were designed and synthesized in order to explore the conformational space of the C-3 pharmacophore. 3-O-Monomethylsuccinyl-betulinic acid (MSB) analogues were also designed to better understand the contribution of the C-3′ dimethyl group of bevirimat (2), the first-in-class HIV maturation inhibitor, which is currently in phase IIb clinical trials. In addition, another triterpene skeleton, moronic acid (MA, 3), was also employed to study the influence of the backbone and the C-3 modification toward the anti-HIV activity of this compound class. This study enabled us to better understand the structure-activity relationships (SAR) of triterpene-derived anti-HIV agents and led to the design and synthesis of compound 12 (EC50: 0.0006 μM), which displayed slightly better activity than 2 as a HIV-1 maturation inhibitor.
- Qian, Keduo,Kuo, Reen-Yun,Chen, Chin-Ho,Huang, Li,Morris-Natschke, Susan L.,Lee, Kuo-Hsiung
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experimental part
p. 3133 - 3141
(2010/09/18)
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- Total synthesis of (+)-neopeltolide
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(Chemical Equation Presented) Rapid elaboration: (+)-Neopeltolide, a novel marine metabolite with potent cytotoxicity against several cancer cell lines, was the target of an efficient total synthesis (see scheme). The construction of the 2,4,6-trisubstituted tetrahydropyran substructure is based on a Suzuki-Miyaura coupling/ring-closing metathesis sequence. BOM = benzyloxymethyl, MPM = 4-methoxyphenylmethyl, TIPS = triisopropylsilyl.
- Fuwa, Haruhiko,Naito, Shinya,Goto, Tomomi,Sasaki, Makoto
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scheme or table
p. 4737 - 4739
(2009/02/06)
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- Total synthesis of herbimycin A
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(Chemical Equation Presented) Hsp90 has recently emerged as a promising biological target for treatment of cancer. Herbimycin A and other members of the benzoquinoid ansamycin class of natural products are known to inhibit Hsp90 activity. The total synthesis of herbimycin A was achieved from the commercially available Roche ester 1 by using allylmetals to control the stereogenic centers at C6, C7, C10, C11, and C12 and a ring-closing metathesis to control the (Z)-double bond of the (E,Z)-dienic moiety.
- Canova, Sophie,Bellosta, Veronique,Bigot, Antony,Mailliet, Patrick,Mignani, Serge,Cossy, Janine
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p. 145 - 148
(2007/10/03)
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- Catalytic asymmetric synthesis of phthioceranic acid, a heptamethyl-branched acid from Mycobacterium tuberculosis
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The first total synthesis of phthioceranic acid (1) has been achieved by an iterative catalytic asymmetric 1,4-addition protocol. This method provides a robust and high-yielding route for the preparation of 1,3-oligomethyl (deoxypropionate) arrays. After the desired number of methyl groups has been introduced, these arrays can be further functionalized at both ends to polymethyl-substituted lipids such as phthioceranic acid, a heptamethyl-branched fatty acid from the virulence factor Sulfolipid-I (2), found in Mycobacterium tuberculosis.
- Ter Horst, Bjorn,Feringa, Ben L.,Minnaard, Adriaan J.
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p. 3013 - 3015
(2008/02/10)
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- The total synthesis and biological properties of the cytotoxic macrolide FD-891 and its non-natural (Z)-C12 isomer
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A total, stereoselective synthesis of the naturally occurring, cytotoxic macrolide FD-891 and of its non-natural (Z)-C12 isomer is described. Three fragments of the main carbon chain were stereoselectively prepared by using asymmetric aldol and allylation reactions as the key steps. The molecule was then assembled by using two Julia-Kocienski olefinations to connect the three fragments and a Yamaguchi reaction to close the macrolactone ring. Some specific biological properties (cytotoxicity, binding to tubulin) have been determined for both macrolides. The E configuration of the C12-C13 olefinic bond seems to be an important feature in determining the cytotoxicity but the precise biological mechanism of the latter still remains to be cleared.
- Garcia-Fortanet, Jorge,Murga, Juan,Carda, Miguel,Marco, J. Alberto,Matesanz, Ruth,Diaz, J. Fernando,Barasoain, Isabel
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p. 5060 - 5074
(2008/02/11)
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- Anti-AIDS agents 73: Structure-activity relationship study and asymmetric synthesis of 3-O-monomethylsuccinyl-betulinic acid derivatives
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3-O-3′(or 2′)-Methylsuccinyl-betulinic acid (MSB) derivatives were separated by using recycle HPLC. The structures of four isomers were assigned by NMR and asymmetric synthesis. 3-O-3′S-Methylsuccinyl-betulinic acid (3′S-MSB, 4) exhibited potent anti-HIV
- Qian, Keduo,Nakagawa-Goto, Kyoko,Yu, Donglei,Morris-Natschke, Susan L.,Nitz, Theodore J.,Kilgore, Nicole,Allaway, Graham P.,Lee, Kuo-Hsiung
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p. 6553 - 6557
(2008/03/18)
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- Synthetic studies toward potent cytotoxic agents amphidinolides G and H: Synthesis of the entire C15-C26 moiety of the top half
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Stereoselective synthesis of the entire (16S, 18S, 21R, 22S, 23R, 25R)- C15-C26 segment 1 of amphidinolides G and H has been achieved for the first time following a highly efficient convergent strategy.
- Chakraborty,Suresh
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p. 7775 - 7778
(2007/10/03)
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- Absolute stereostructure of callystatin A, a potent cytotoxic polyketide from the marine sponge, Callyspongia truncata
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The unidentified configurations at C5 and C10 incallystatin A (1), a potent cytotoxic polyketide from the marine sponge Callyspongia truncata, were determined to be R,R by comparing the circular dichroism spectrum of 1 with those of two model compounds 2 and 3. Compounds 2 and 3 were synthesized by using E-selective Wittig olefination at the C6-C7 position as a key reaction.
- Murakami, Nobutoshi,Wang, Weiqi,Aoki, Masashi,Tsutsui, Yasuhiro,Higuchi, Kouichi,Aoki, Shunji,Kobayashi, Motomasa
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p. 5533 - 5536
(2007/10/03)
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- Synthesis of optically active diastereomers of a nonproteic neurotrophic mimetic
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The four diastereomers 3, elongated analogues of perhydroretinol, are synthesized starting from both optically pure 3-bromo-2-methyl-1-propanol enantiomers. All exhibit neurotrophic activity on cultured neuronal cells derived from fetal rat cerebral hemispheres.
- Keyling-Bilger, Florence,Schmitt, Gaby,Beck, Alain,Luu, Bang
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p. 14891 - 14904
(2007/10/03)
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- Total Synthesis of (-)-Stemoamide
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An enantiocontrolled total synthesis of the tricyclic alkaloid, stemoamide (2), is reported. Key Words: Asymmetric aldol; chiral butyrolactone synthesis; selective 1,3-acyclic diol formation.
- Williams, David R.,Reddy, Jayachandra P.,Amato, George S.
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p. 6417 - 6420
(2007/10/02)
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- Studies directed toward the total synthesis of tetronolide 1. An enantioselective synthesis of the octahydronaphthalene unit
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An efficient enantioselective route to the octahydronaphthalene unit present in tetronolide (1), the stereochemically complex aglycone common to the tetrocarcins, a novel group of antitumor substances, is described. The sequence employs the intramolecular
- Boeckman Jr., Robert K.,Barta, Thomas E.,Nelson, Scott G.
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p. 4091 - 4094
(2007/10/02)
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- AN ENANTIOSELECTIVE SYNTHESIS OF THE C(10) TO C(23) BACKBONE OF THE POTENT IMMUNOSUPPRESSANT FK506
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The C(10) to C(23) fragment of FK506 has been pepared in a convergent, highly stereocontrolled, fashion.The key transformations entailed opening of a symmetrical trans-disubstituted epoxide with a trisubstituted vinylalane ate complex, the reductive remov
- Smith III, Amos B.,Hale, Karl J.
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p. 1037 - 1040
(2007/10/02)
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