4525-28-4Relevant academic research and scientific papers
Total syntheses of (±)-melicolones A and B
Martin, Stephen F.,Wang, Zhipeng
, p. 9071 - 9074 (2020)
The first total syntheses of (±)-melicolones A and B, which have a unique and densely functionalized framework derived from a rearranged prenylated acetophenone, were accomplished in 12.3% combined overall yield. The concise and divergent synthesis of these two natural products, which were isolated in racemic form, was achieved in a longest linear sequence requiring only 9 steps (11 total steps) and 8 isolated intermediates using commercially available starting materials. This approach, which might enable access to all tetracyclic melicolones, features the highly regioselective (16:1) and diastereoselective (15:1) dipolar cycloaddition of a carbonyl ylide generated by the unusual cyclization of a rhodium carbene with the carbonyl oxygen atom of an aliphatic aldehyde. This cycloaddition proceeds with dominant steric control to give a highly functionalized oxabicycloheptane core. Stereoselective enolate alkylation led to a prenylated intermediate that underwent an intramolecular aldol reaction to give the penultimate tricyclic intermediate. Tandem epoxidation of the pendant prenyl group followed by a regioselective, acid-catalyzed cyclization delivered (±)-melicolones A and B.
Concise stereoselective and stereodivergent syntheses of (±)-melicolones A and B
Wang, Zhipeng,Martin, Stephen F.
, (2021/11/26)
The first total syntheses of the epimeric (±)-melicolones A and B, which are bioactive constituents isolated as racemates from the leaves of Melicope ptelefolia, were achieved in 12.3% combined overall yield. The divergent approach to these unusual natural products is remarkably concise and required a longest linear sequence of only nine steps (11 total steps) from commercially available starting materials. The significant synthetic challenge posed by the unique and densely functionalized polycyclic framework characteristic of the melicolones was addressed by a novel and highly regioselective (16:1) and diastereoselective (15:1) dipolar cycloaddition to deliver the oxabicycloheptane core. This pivotal reaction featured an innovative combination of an unsaturated vinylogous ester dipolarophile with a carbonyl ylide that was generated by an unusual cyclization of the carbonyl oxygen atom of an aliphatic aldehyde with a rhodium carbenoid. Stereoselective prenylation of the ketone enolate derived from this bicyclic core gave an intermediate that was processed via a one-pot O-demethylation cycloaldolization sequence to give the penultimate intermediate. The synthesis was completed by a bioinspired tandem epoxidation of the prenyl substituent followed by a regioselective, acid-catalyzed cyclization to deliver (±)-melicolones A and B. This approach may be applicable to the syntheses of other melicolones having a tetracyclic core.
Total Synthesis of Ajudazol A by a Modular Oxazole Diversification Strategy
Essig, Sebastian,G?lz, Jan Philipp,Menche, Dirk,Von Schwarzenberg, Karin,Wollnitzke, Philipp
supporting information, (2020/09/02)
The total synthesis of the potent respiratory chain inhibitor ajudazol A was accomplished by a concise strategy in 17 steps (longest linear sequence). The modular approach was based on a direct oxazole functionalization strategy involving a halogen dance
Isobenzofurans as Synthetic Intermediates: Synthesis and Biological Activity of 8-epi-(–)-Ajudazol B
Adair, Liam,Egan, Ben A.,Pearson, Colin M.,Lopez-Gonzalez, Ricardo,Kuchar, Michal,Mendoza-Mendoza, Artemio,Prunet, Jo?lle,Marquez, Rodolfo
supporting information, p. 6661 - 6672 (2020/10/15)
Ajudazol B is a polyketide secondary metabolite, isolated from the myxobacterium Chondromyces crocatus, that exhibits potent biological activity. Herein, we report a convergent total synthesis of 8-epi-(–)-ajudazol B. The key step is a regio-selective alk
Divergent asymmetric total synthesis of all four pestalotin diastereomers from (R)-glycidol
Moriyama, Mizuki,Nakata, Kohei,Fujiwara, Tetsuya,Tanabe, Yoo
, (2020/01/28)
All four chiral pestalotin diastereomers were synthesized in a straightforward and divergent manner from common (R)-glycidol. Catalytic asymmetric Mukaiyama aldol reactions of readily-available bis(TMSO)diene (Chan’s diene) with (S)-2-benzyloxyhexanal der
Stereoselective formation of (E)-β-alkoxy acrylates from fischer carbene complexes and chelated amino acid ester enolates
Chaudhuri, Rupsha,Kazmaier, Uli
, p. 693 - 695 (2014/04/03)
Chelated amino acid ester enolates react with alkyl Fischer carbene complexes via nucleophilic attack on the electrophilic carbene center. Subsequent elimination of the metal fragment and trifluoroacetamide results in the formation of β-alkoxy-α,β-unsaturated esters in a highly E-stereoselective fashion. Georg Thieme Verlag Stuttgart. New York.
Full stereochemical determination of ajudazols a and b by bioinformatics gene cluster analysis and total synthesis of ajudazol B by an asymmetric ortholithiation strategy
Essig, Sebastian,Bretzke, Sebastian,Müller, Rolf,Menche, Dirk
supporting information, p. 19362 - 19365 (2013/02/21)
The stereochemical determination of the potent respiratory chain inhibitors ajudazols A and B and the total synthesis of ajudazol B are reported. Configurational assignment was exclusively based on biosynthetic gene cluster analysis of both ketoreductase
Iridium-catalyzed asymmetric hydrogenation of vinyl ethers
Zhu, Ye,Burgess, Kevin
supporting information; experimental part, p. 979 - 983 (2009/05/30)
A carbene-oxazoline catalyst 1 proved to be an effective catalyst for reduction of an enol ether that the literature suggested could not be hydrogenated effectively by P,N-Ir catalysts. Thus, a series of ester and alcohol substrates were hydrogenated using catalyst 1. Good to excellent enantioselectivities and high conversions were obtained.
Synthesis of the eastern portion of ajudazol a based on stille coupling and double acetylene carbocupration
Krebs, Oliver,Taylor, Richard J. K.
, p. 1063 - 1066 (2007/10/03)
(Chemical Equation Presented) A strategy for the synthesis of ajudazol A, an unusual, pharmacologically active metabolite from myxobacteria, based on the Stille cross-coupling of a 2-stannyl-oxazole with a vinyl iodide unit is described; the vinyl halide unit containing a (Z,Z)-diene was prepared in one pot by the double acetylene carbocupration of a functionalized alkyl cuprate followed by trapping with 2,3-dibromopropene.
Pigments of fungi. Part 68. Synthesis and absolute configuration of thysanone2
Donner, Christopher D.,Gill, Melvyn
, p. 938 - 948 (2007/10/03)
The (1R,3S)-absolute stereochemistry of thysanone 1, a fungal benzoisochromanquinone with potent human rhinovirus 3C-protease inhibitory activity, is established for the first time by total synthesis of the natural product from ethyl (S)-lactate and CD co
