Alkene−Alkyne Coupling as a Linchpin:  An Efficient and Convergent Synthesis of Amphidinolide P

Trost, Barry M.; Papillon, Julien P. N.

doi:10.1021/ja045449x

Cited by 57 publications

(21 citation statements)

References 27 publications

(29 reference statements)

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“…(Scheme ). 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 DMF/MeOH furnished ( E )‐iodoalkenol 11 with perfect stereoselectivity in good yield.…”

Section: Methodsmentioning

confidence: 99%

Total Synthesis of Neooxazolomycin

et al. 2007

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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.

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Section: Methodsmentioning

confidence: 99%

Total Synthesis of Neooxazolomycin

et al. 2007

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“…61, 62 Here, they targeted alkene–alkyne coupling technology for the establishment of the C10–C11 bond. As illustrated in Figure 18B, success was seen in the union of β-lactone containing enyne 37 with terminal alkyne 38 – a process that delivered 39 in 75% yield with high levels of selectivity.…”

Section: Alkene–alkyne Cross-couplingmentioning

confidence: 99%

Metallacycle-mediated cross-coupling in natural product synthesis

2016

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“…To execute the synthesis of neooxazolomycin ( 2 ) along the strategy shown in Scheme , we first addressed the stereocontrolled synthesis of key intermediate 21 , and we initially came up with an approach that relied on palladium‐catalyzed cyclization of iodide 20 (Scheme ). Thus, homopropargyl alcohol 15 was first prepared by the coupling of 13 and 14 , both readily available from methyl ( S )‐3‐hydroxy‐2‐methylpropanoate, and then its regio‐ and stereoselective transformation to 18 was carefully investigated according to the method developed by Tamao et al . The initial intramolecular hydrosilylation reaction of 16 , prepared in situ from 15 , was found to proceed quantitatively using Pt(dvds) as a catalyst, while commonly used H 2 PtCl 6 ·H 2 O did not promote the reaction at all.…”

Section: Synthesis Of Neooxazolomycinmentioning

confidence: 99%

Total Synthesis of Oxazolomycins

Ishihara

Hatakeyama

2014

The Chemical Record

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The oxazolomycin family of antibiotics, isolated from several Streptomyces strains, are intriguing molecules for synthesis due to their characteristic oxazole polyene lactam-lactone structures and significant antiviral, antibacterial, and antitumor biological activities. In the last ten years, we have been addressing synthetic problems to accomplish the total syntheses of neooxazolomycin and oxazolomycin A as well as the related antibiotics, inthomycins A, B, and C, which have truncated structures corresponding to the left-hand fragments. This account describes an overview of our synthetic efforts toward these natural products focusing on the strategies and methodologies we devised.

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Alkene−Alkyne Coupling as a Linchpin: An Efficient and Convergent Synthesis of Amphidinolide P

Cited by 57 publications

References 27 publications

Total Synthesis of Neooxazolomycin

Total Synthesis of Neooxazolomycin

Metallacycle-mediated cross-coupling in natural product synthesis

Total Synthesis of Oxazolomycins

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