Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin

Makabe, Hidefumi; Higuchi, Masaharu; Konno, Hiroyuki; Murai, Masatoshi; Miyoshi, Hideto

doi:10.1016/j.tetlet.2005.04.144

Cited by 17 publications

(5 citation statements)

References 19 publications

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“…The chosen route relied on Brown's hydroxy-crotylation technology . Thus, treatment of aldehyde 19 (prepared from 4-pentyn-1-ol in two steps, 90% yield) with in situ-generated [( Z )-γ-(methoxymethoxy)allyl]-(−)-diisopinocampheylborane, [(−)- 20 ], (from methoxymethyl allyl ether, s- BuLi, (−)-Ipc 2 BOMe and BF 3 ·OEt 2 ) in THF at −78 to 23 °C afforded, upon desilylation (K 2 CO 3 , MeOH), hydroxy acetylene 21 in good overall yield (78% for the two steps) and excellent diastereoselectivity [>95% de, 1 H NMR spectroscopic analysis (600 MHz); >90% ee, 1 H NMR (600 MHz) analysis of the corresponding R and S Mosher esters] . Attachment of the carbamate group [Cl 3 CC(O)NCO, K 2 CO 3, MeOH, 100% yield] onto alcohol 21 followed by treatment with NBS and AgNO 3 furnished bromide 23 (90% yield) through acetylenic 22 .…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of the Originally Proposed and Revised Structures of Palmerolide A and Isomers Thereof

et al. 2008

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Palmerolide A is a recently disclosed marine natural product possessing striking biological properties, including potent and selective activity against the melanoma cancer cell line UACC-62. The total syntheses of five palmerolide A stereoisomers, including the originally proposed (1) and the revised [ent-(19-epi-20-epi-1)] structures, have been accomplished. The highly convergent and flexible strategy developed for these syntheses involved the construction of key building blocks 2, 19-epi-2, 20-epi-2, ent-2, 3, ent-3, 4, and ent-4, and their assembly and elaboration to the target compounds. For the union of the building blocks, the Stille coupling reaction, Yamaguchi esterification, Horner-Wadsworth-Emmons olefination, and ring-closing metathesis reaction were employed, the latter being crucial for the stereoselective formation of the macrocycle of the palmerolide structure. The Horner-Wadsworth-Emmons olefination and the Yamaguchi lactonization were also investigated and found successful as a means to construct the palmerolide macrocycle. The syntheses were completed by attachment of the enamide moiety through a copper-catalyzed coupling process.

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Section: Resultsmentioning

confidence: 99%

Total Synthesis of the Originally Proposed and Revised Structures of Palmerolide A and Isomers Thereof

et al. 2008

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“…Scheme depicts the construction of the stannane fragment 3 . Reaction of aldehyde 9 (prepared in 2 steps from 4‐pentyn‐1‐ol by standard methods)8 with [( Z )‐γ‐(methoxymethoxy)allyl]‐(−)‐diisopinocampheylborane ( 10 , freshly prepared from methoxymethyl allyl ether, s BuLi, (−)‐Ipc 2 BOMe and BF 3 ⋅Et 2 O)9 in THF at −78 °C afforded, upon desilylation (K 2 CO 3 /MeOH), the hydroxy acetylene 11 in good overall yield (74 % for the 2 steps) and excellent stereoselectivity (>95 % de (NMR) and >90 % ee (Mosher ester)). Finally, installation of the carbamate group (Cl 3 CC(O)NCO/K 2 CO 3 /MeOH, quant.…”

Section: Methodsmentioning

confidence: 99%

Total Synthesis of the Originally Proposed and Revised Structures of Palmerolide A

et al. 2007

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Palmerolide A (Figure 1) is a recently reported polyketide secondary metabolite with an impressive molecular architecture and biological profile.[1] This marine natural product was isolated from the circumpolar tunicate Synoicum adareanum, which is commonly found in the shallow waters around Anvers Island on the Antarctic Peninsula, and exhibits unusual selectivity against a number of cell lines in the 60 cell panel of the National Cancer Institute (NCI). Specifically, palmerolide A was found to exhibit potent activity against the melanoma cell line UACC-62 (LC 50 = 18 nm), only modest cytotoxicity against the colon cancer cell line HCC-2998 (LC 50 = 6.5 mm) and the renal cancer cell line RXF 393 (LC 50 = 6.5 mm), and virtually no effect (LC 50 > 10 mm) against other cell lines, thus demonstrating a selectivity index of 10 3 among the cell lines tested. Interestingly, palmerolide A displayed an activity profile in the NCI 60 cell line panel that correlated with that of vacuolar ATPase inhibitors. [2] Palmerolide A was shown to inhibit V-ATPase with an IC 50 value of 2 nm and to be active in the NCIs hollow fiber assay. The intriguing biological properties of palmerolide A, along with its relative scarcity, prompted us to undertake its chemical synthesis.Inspection of the proposed structure of palmerolide A (1 a) reveals a 20-membered macrolide, an enamide-containing side chain, 7 olefinic bonds (3 of which are trisubstituted), and a carbamate moiety. Based on detailed NMR spectroscopic analysis, the relative and absolute configuration of this natural product was put forward as that shown in structure 1 a (Figure 1), although the structural assignments at C19 and C20 were not error proof. Specifically, while the NOE interactions and coupling constants exhibited by palmerolide A may exclude the two anti C19/C20 diastereomers, both syn structures could be possible. Furthermore, while Mosher ester studies suggested the absolute stereochemistry at the C7, C10, and C11 positions, the low optical rotation of the natural product [1] did not bode well for its diagnostic value as a means to confirm its absolute stereochemistry. Most recently, these suspicions were confirmed by an elegant study by De Brabander and co-workers (which culminated in the total synthesis of the unnatural enantiomer of palmerolide A), [3] with the structural revision of not only the relative stereochemistry between the C7-C11 and C19-C20 domains, but also of the absolute configuration of the molecule. Herein, we report our own efforts in this area that culminated in total syntheses of, among several isomers, the originally proposed structure 1 a and the revised structure 1 b (Figure 1) of palmerolide A by a modular and flexible strategy that allows access to variants of the palmerolide A molecule as depicted retrosynthetically in Scheme 1.It was envisioned that a Stille coupling reaction, a Yamaguchi esterification, a ring-closing metathesis, and an enamide coupling reaction would serve to assemble and

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“…This concise metathesis-based synthesis was accomplished in 12 steps and 9% overall yield from hexa-1,5-diene-3,4-diol 184. The same year in 2005, Makabe and co-workers [81] developed a convergent synthesis of rollicosin (183 a) and its diastereomer 15,16-bis-epi-rollicosin (183 a') through asymmetric dihydroxylation and Sonogashira coupling as key steps. In a subsequent full account [82] in 2006, along with same rollicosin synthesis, the strategy was extended to the synthesis of squamostolide (183 b) (Scheme 25).…”

Section: Synthesis Of Rollicosin and Squamostolidementioning

confidence: 99%

Muricatacin, a Gateway Molecule to Higher Acetogenin Synthesis

Fernandes

Bhowmik

Choudhary

2020

Chemistry An Asian Journal

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In this review, we have abstracted the various syntheses of acetogenins where the start point has been muricatacin. The latter can best be synthesized in either enantiomer form by the Sharpless method in three steps and can be admired as a gateway molecule for a quick assembly of many higher acetogenins. Muricatacin with orthogonally differentiated hydroxy groups and the available lactone carbonyl for chain elongation/modification can enable the concise synthesis of higher acetogenins. Many closely related synthetic intermediates possible from muricatacin are also abstracted here. The review should give impetus for future synthetic endeavours where the start point could be muricatacin and at least to the new molecules that are yet to be synthesized.

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Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin

Cited by 17 publications

References 19 publications

Total Synthesis of the Originally Proposed and Revised Structures of Palmerolide A and Isomers Thereof

Total Synthesis of the Originally Proposed and Revised Structures of Palmerolide A and Isomers Thereof

Total Synthesis of the Originally Proposed and Revised Structures of Palmerolide A

Muricatacin, a Gateway Molecule to Higher Acetogenin Synthesis

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