The Synthesis of Two Furan‐Based Analogues of the α′,β′‐Epoxy Ketone Proteasome Inhibitor Eponemycin

Abstract

Myers's methodology for enantioselective amino acid synthesis was employed to prepare the N-Boc didehydroleucine amide derivative 15 and to effect its conversion into the acylfuran intermediate 17. Coupling of 19 (R = H) with N-(isooctanoyl)serine provided the furan-based analogue 4 of eponemycin (de = 96 %), a peptide epoxide with potent cyto-

A Synthetic Approach to the Channel Complex Structure of Antibiotic in a Membrane: Backbone ¹⁹F-Labeled Amphotericin B for Solid-State NMR Analysis

“…The uoroole nation by HWE reaction with a commercially available uorophosphonate reagent (13) proceeded well to give the E uoroole n 12 stereoselectively. After the conversion of the ester into aldehyde in two steps, the second ole n elongation with allylic phosphonate 16 33 successfully furnished trienoate 15EEE, which was then isomerized to the desired trienoate 15ZEE through a treatment with catalytic diphenyldiselenide under re ux condition 27 and the EE ether reformation of the partially deprotected hydroxy group. After the transformation of ester to aldehyde, the third HWE reaction with the separately prepared stannyl phosphonate 17 34 proceeded smoothly to afford the desired uorinated C22 C37 segment (6) as a single isomer in acceptable yields.…”

Total Synthesis of δ-Sanshool and Analogues Thereof

“…tan-1-ol, which without further purification was condensed with phosphonate 6 13 in the presence of LiOH in THF at reflux temperature 11 to give a mixture of the dienes 7 and 8. The ratio of dienes 7/8, evaluated by 1 H NMR analysis of the crude mixture, was 5:1 with a total yield of 46% of the E-isomer 7 (calculated over two steps).…”

“…Phosphonates 6, 18 and 19 were prepared from ethyl 4bromocrotonate by an Arbuzov reaction, 13 hydrolysis of the ester moiety 15 and subsequent reaction of carefully dried acid 22 with the appropriate amine in the presence of EDC and HOBt (Scheme 4). 11 The double bond geometry of the new compounds was assigned by decoupling experiments and comparison of the 1 H NMR spectrum of synthesized δ-sanshool with data reported in the literature (see the Supporting Information).…”

A New Route for the Total Synthesis of 6,7‐Dihydroeponemycin

“…[3Ϫ6] In the preceding paper [7] the synthesis of two new furan analogues of eponemycin was described, wherein methodology developed by Myers and co-workers [8Ϫ15] was employed for both the preparation of the didehydroleucine derivative 3 (R ϭ Boc) and its subsequent reaction with 2-furyllithium. As an extension of this approach we envisaged that by reaction of amide 3 with the organolithium reagent 4 the key amino ketone intermediate 5 would be obtained (Scheme 1).…”

“…[7] As feared, Fmoc deprotection by treatment of 18a with Et 3 N, DBU or Hunigs base was followed by instantaneous opening of the epoxide ring by the liberated amine. A subsequent (and unsuccessful) attempt was made to intercept the liberated amine before the intramolecular ring-opening/ ring-forming process could occur, by ensuring that the activated acid component [PyBOP, HOBT] was present in the reaction medium at the moment when the amine base was added.…”