Incubation of opsin with synthetic 6-s-locked retinoids 2a and 2b only led to pigment formation from the alpha-locked 2a, the CD spectrum of which was similar to that of native rhodopsin (Rh). This establishes that the 6-s-bond of the chromophore in rhodopsin is cis, and that its helicity is negative. Earlier cross-linking studies showed that the 11-cis to all-trans photoisomerization occurring in the batho-Rh to lumi-Rh conversion induces a flip over of the side carrying the ring moiety. The GTP-binding assay of pigment Rh-(2a), incorporating retinal analogue 2a, has shown that its activity is 80% that of the native pigment. That is, the overall conformation around the 6-s bond is retained in the steps leading to G-protein activation.

The first total synthesis of oxazolomycin A, a structurally novel oxazole polyene γ-lactam/β-lactone antibiotic, is described. Key features include the stereocontrolled construction of the right-hand heterocyclic core by taking advantage of an In(III)-catalyzed Conia-ene type cyclization and the asymmetric synthesis of the left-hand segment starting with a Cinchona alkaloid-catalyzed cyclocondensation of an aldehyde with an acid chloride.

The total syntheses of (+)-inthomycin A, (+)-inthomycin B and (-)-inthomycin C, the oxazole-triene antibiotics isolated from Streptomyces sp., have been accomplished via the highly enantio- and stereoselective construction of the C1-C7 (iododienyl)aldol units by taking advantage of a Cinchona alkaloid-catalyzed asymmetric β-lactone synthesis and their isomerisation-free Stille coupling with (E)-5-(3-(tributylstannyl)allyl)oxazole.

No abstract

Conica can: The In(OTf)3‐catalyzed cyclization of nitrogen‐ and oxygen‐tethered acetylenic malonic esters gives five‐ to seven‐membered heterocycles in moderate to excellent yields (see scheme; Tf=trifluoromethanesulfonyl). The asymmetric synthesis of (−)‐salinosporamide A illustrates the synthetic utility of the method.

Dedicated to Professor Yoshito Kishi on the occasion of his 70th birthdayNeooxazolomycin and oxazolomycin A, originally isolated from a strain of Streptomyces by Uemura and co-workers in 1985, [1] together with the seven other congeners identified to date constitute a family of structurally unique oxazole polyene lactam-lactone antibiotics. These oxazolomycins were found to exhibit wide-ranging and potent antibacterial and antiviral activities as well as in vivo antitumor activity. Their intriguing molecular architectures and biological activities make these compounds attractive targets for synthesis. [2,3] In 1990, Kende et al. disclosed the synthesis of neooxazolomycin, [4] and this superb achievement is the first and only total synthesis of any member of this family; however the stereocontrolled construction of the right-hand core has remained an unanswered challenge.Our synthetic plan for neooxazolomycin makes a disconnection at the amide linkage to give the left-hand segment 1 and right-hand segment 2 (Scheme 1). Since Kende et al. had already demonstrated an effective method for the synthesis of 1 [4] by a Reformatsky-type aldol reaction [5] and Stille coupling, [6] the major challenge in the synthesis resided in the stereoselective construction of 2. From the retrosynthetic perspective, we envisioned pyrrolidinone 4 as a precursor of 2 with considerably less structural complexity which would lead to 2 through a Nozaki-Hiyama-Kishi reaction [7] and stereoselective dihydroxylation with concomitant lactonization. We postulated that this precursor could be accessed by a palladium-catalyzed cyclization of amide 5. This approach is particularly appealing since the three contiguous stereogenic centers including two quaternary centers could be created by one dihydroxylation process. The required amide 5 was synthesized in a completely stereoselective manner by taking advantage of the intramolecular hydrosilylation [8] developed by Tamao et al. [9] (Scheme 2). Thus, alkynol 8 was first prepared by the coupling of alkyne 6 [10] and triflate 7, [11] both readily available from (S)hydroxy-2-methylpropanoate, followed by desilylation. Reaction of 8 with tetramethyldisilazane provided hydrodimethylsilyl ether 9, which upon hydrosilylation with [Pt(dvds)] [12] as a catalyst in THF at room temperature followed by exposure of the resulting siloxane 10 to iodine in the presence of CsF in Scheme 1. Retrosynthetic analysis of neooxazolomycin. Bn = benzyl, Fmoc = 9-fluorenylmethyloxycarbonyl.

No abstract

A facile chromatography-free route to Kang's intermediate for the synthesis of (+)-lactacystin, a potent proteasome inhibitor, has been developed starting with Brown's asymmetric crotylation of tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate, easily available from 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris).