- Formal total synthesis of (+)-methynolide
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A formal total synthesis of (+)-methynolide was achieved in 23 steps highlighted by a crotylboration, a ring-closing metathesis, a Sharpless kinetic resolution of an allylic alcohol and a Takai reaction.
- Cossy, Janine,Bauer, David,Bellosta, Véronique
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- Practical Protocols for the Preparation of Highly Enantioenriched Silyl Ethers of (R)-3-Hydroxypentan-2-one, Building Blocks for the Synthesis of Macrolide Antibiotics
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Methacrolein is transformed in three steps to (R)-3-tert-butyldiphenylsilyloxypentan-2-one or (R)-3-tert-butyldimethylsilyloxypentan-2-one, compounds which serve as building blocks for the construction of macrolide antibiotics. The route is practical, highly enantioselective, and easily scaled.
- Seiple, Ian B.,Hog, Daniel T.,Myers, Andrew G.
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Read Online
- Formal total synthesis of (+)-methynolide
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A convergent total synthesis of (+)-methynolide was achieved in 23 steps highlighted by a ring-closing metathesis, a Takai reaction, a Sharpless kinetic resolution of an allylic alcohol and a crotylboration.
- Cossy, Janine,Bauer, David,Bellosta, Ve?ronique
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Read Online
- Ambruticins: tetrahydropyran ring formation and total synthesis
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The ambruticins are a family of polyketide natural products which exhibit potent antifungal activity. Gene knockout experiments are in accord with the proposal that the tetrahydropyran ring of the ambruticins is formedviathe AmbJ catalysed epoxidation of the unsaturated 3,5-dihydroxy acid, ambruticin J, followed by regioselective cyclisation to ambruticin F. Herein, a convergent approach to the total synthesis of ambruticin J is described as well as model studies involving epoxidation and cyclisations of unsaturated hydroxy esters to give tetrahydropyrans and tetrahydrofurans. The total synthesis involves preparation of three key fragments which were unitedviaa Suzuki-Miyaura cross-coupling and Julia-Kocienski olefination to generate the required carbon framework. Global deprotection to a triol and selective oxidation of the primary alcohol gave, after hydrolysis of the lactone, ambruticin J.
- Bowen, James I.,Crump, Matthew P.,Wang, Luoyi,Willis, Christine L.
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supporting information
p. 6210 - 6215
(2021/07/28)
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- Large-scale preparation of key building blocks for the manufacture of fully synthetic macrolide antibiotics
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Key building blocks for the production of fully synthetic macrolides have been scaled-up in first time pilot plant and kilo-lab campaigns. These building blocks have supported the discovery of new macrolide antibiotics as well as ongoing preclinical studies.
- Hogan, Philip C.,Chen, Chi-Li,Mulvihill, Kristen M.,Lawrence, Jonathan F.,Moorhead, Eric,Rickmeier, Jens,Myers, Andrew G.
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p. 318 - 325
(2018/03/21)
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- 14-MEMBERED KETOLIDES AND METHODS OF THEIR PREPARATION AND USE
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Provided herein are methods of preparing new 14-membered ketolides via coupling of an eastern and western half moiety, followed by macrocyclization, and optional functionalization. Intermediates in the synthesis of these ketolides including the eastern and western halves are also provided. Pharmaceutical compositions and methods of treating infectious diseases and inflammatory conditions using these ketolides are also provided.
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Paragraph 00591
(2016/05/02)
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- MACROLIDES AND METHODS OF THEIR PREPARATION AND USE
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Provided herein are methods of preparing macrolides by the coupling of an eastern and western half, followed by macrocyclization, to provide macrolides, including both known and novel macrolides. Intermediates in the synthesis of macrolides including the eastern and western halves are also provided. Pharmaceutical compositions and methods of treating infectious diseases and inflammatory conditions using the inventive macrolides are also provided. A general diastereoselective aldol methodology used in the synthesis of the western half is further provided.
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Paragraph 00675
(2014/10/18)
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- Amaranzoles B?F, imidazole-2-carboxy steroids from the marine sponge phorbas amaranthus. C24- N - And C24- O -analogues from a divergent oxidative biosynthesis
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Five new steroidal imidazoles, amaranzoles B?F, were isolated from extracts of the marine sponge Phorbas amaranthus along with the known amaranzole A. The C24-N-(4-p-hydroxyphenyl)imidazol-5-yl constitution found in amaranzoles A, C, and D is replaced by a C24-O-(4-p-hydroxyphenyl)imidazole-2-carboxylate motif in amaranzoles B, E, and F. The structures were elucidated by interpretation of spectroscopic data. The C24 side chain configuration was assigned by synthesis of a model ester followed by chiroptical comparisons of its CD spectrum with that of an amaranzole B derivative.
- Morinaka, Brandon I.,Pawlik, Joseph R.,Molinski, Tadeusz F.
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scheme or table
p. 2453 - 2460
(2010/07/17)
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- Enantioselective synthesis of allylic alcohols via an oxazaborolidinium ion catalyzed diels-alder/retro-diels-alder sequence
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A triflimide-activated oxazaborolidine catalyst successfully promoted the asymmetric Diels-Alder reaction of 9-methylanthracene with methacrolein in high regio- and enantioselectivity. The cycloadduct obtained was subsequently used as a chiral template to
- Jones, Simon,Valette, Damien
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supporting information; experimental part
p. 5358 - 5361
(2010/01/19)
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- Total synthesis of jerangolid D
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A short and convergent synthesis of jerangolid D is described. As key steps, a Blaise reaction is employed to construct the lactone ring, a diastereoselective multicomponent Sakurai condensation leads to the dihydropyran ring, and the skipped diene is ass
- Pospisil, Jiri,Marko, Istvan E.
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p. 3516 - 3517
(2008/01/01)
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- Total synthesis of (+)-ambruticin S
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A convergent total synthesis of the novel antifungal agent ambruticin S (1) has been completed from the assembly of intermediates 18, 33 and 52 that served as the respective A-, B-, and C-ring precursors. The first generation approach to a potential A-ring intermediate eventuated in the synthesis of 9a via a route that featured oxidation of the dihydroxy furan 2 and elaboration of the dihydropyranone 3 derived therefrom. Although 9a served as a precursor of 31E to complete a formal synthesis of 1, there were several inefficiencies associated with the preparation of 9a. A more expedient and efficient route to an A-ring subunit was devised that commenced with the carbohydrate-derived bisacetonide aldehyde 10 and produced 18 in five steps and 46% overall yield. The synthesis of the cyclopropyl sulfone 33 was initiated with the enantioselective cyclopropanation of 19 catalyzed by Rh 2[5(S)-MEPY]4. Ring opening of the resultant lactone 20 followed by a series of refunctionalizations gave 33 in a total of seven steps and 46% yield from 19. Coupling of the A- and B-ring precursors 18 and 33 was then achieved via a modified Julia coupling followed by deprotection and oxidation to furnish the key intermediate 35. The dihydropyran core of the C-ring subunit precursor 49 was formed from the ring closing metathesis of the diene 48, which was prepared in three steps from the known epoxide 45, followed by oxidation. A chelation-controlled addition to the methyl ketone 49 set the stage for a stereoselective [2,3]-Wittig rearrangement that delivered the alcohol 51 that was then transformed in two steps to the sulfone 52. A traditional Julia coupling of 52 and 35 proceeded with excellent stereoselectivity, and subsequent removal of the various protecting groups gave ambruticin S (1). The longest linear sequence was 13 steps and proceeded in 4. 3% overall yield.
- Berberich, Stephen M.,Cherney, Robert J.,Colucci, John,Courillon, Christine,Geraci, Leo S.,Kirkland, Thomas A.,Marx, Matthew A.,Schneider, Matthias F.,Martin, Stephen F.
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p. 6819 - 6832
(2007/10/03)
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- An amino alcohol ligand for highly enantioselective addition of organozinc reagents to aldehydes: Serendipity rules
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(matrix presented) Amino alcohol 4 (or its enantiomer) is prepared in two simple steps. Commercial (1R,2S)-2-amino-1,2-diphenylethanol is dialkylated with bis(2-bromoethyl) ether. Subsequent hydrogenation over 5% Rh on alumina in the presence of morpholine unexpectedly stops at the hexahydro derivative 4. Amino alcohol 4 promotes the enantioselective addition of diethylzinc to aldehydes at room temperature in up to 99% enantiomeric excess.
- Nugent, William A.
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p. 2133 - 2136
(2007/10/03)
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- An Efficiente Preperation of Optically Active Allylic Alcohols, 2-Furyl Alcohols and 2-Thienyl Alcohols by Catalytic Asymmetric Alkylation
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Highly enantioselective alkylation of some kinds of α,β-unsaturated aldehydes with dialkylzinc proceed in the presence of a small amount of a chiral β-amino alcohol, thus providing an efficient method of obtaining optically active secondary allylic alcohols.Optically active 2-furyl and 2-thienyl alcohols are also available by this catalytic asymmetric alkylation method.
- Hayashi, Masahiko,Kaneko, Toshiyuki,Oguni, Nobuki
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- Stereospecific Telluride-Mediated Conversion of Glycidols to Allyl Alcohols: An Extension of the Sharpless Kinetic Resolution
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Treatment of methanesulfonate esters of terminal glycidols obtained by epoxidation in the Sharpless kinetic resolution (SKR) of 1-substituted 2-propenols (secondary allyl alcohols) with telluride ion (Te2-) converts the glycidols to allyl alcohols of the same stereochemical configuration as the unreacted enantiomer from the SKR.
- Discordia, Robert P.,Dittmer, Donald C.
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p. 1414 - 1415
(2007/10/02)
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