Synthesis of the Macrocyclic Core of Iriomoteolide 3a

Reddy, Chada Raji; Dharmapuri, Gajula; Rao, N. Nageswara

doi:10.1021/ol9025183

Cited by 34 publications

(17 citation statements)

References 33 publications

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“…[a] D = -9.14 (c 1.28, CHCl 3 ); IR (neat) 2985,2956,2931,2858,1738,1589,1459,1429,1369,1112 3,135.5,133.1,129.6,129.4,127.6,108.7,81.3,78.5,62.5,51.3,40.8,39.3,30.0,27.1,26.9,29.7,19.5,19.2;MS (FAB) …”

Section: Experimental Olefin Cross-metathesis Of Alkene 2 and Methyl mentioning

confidence: 99%

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Efficient Synthesis of the C1‐C9 Fragment of 7,8‐O‐Isopropylidene Protected Iriomoteolide 3a Derivative

Chang

2011

J Chinese Chemical Soc

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An efficient and stereoselective synthesis of the C1-C9 moiety of the 7,8-O-isopropylidene protected iriomoteolide 3a derivative has been accomplished. In our strategy, we employed olefin cross-metathesis of the L-(+)-tartaric acid derivative (((4S,5S)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)methoxy)(tert-butyl)diphenylsilane with a synthesized methyl (S)-3-methylhex-5-enate to successfully provide the correct olefin geometry of the desired fragment.

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Section: Experimental Olefin Cross-metathesis Of Alkene 2 and Methyl mentioning

confidence: 99%

“…In this work, the C1-C9 fragment was synthesized in eight steps in 34% yield from (S)-(-)-citronellol. 3 Herein, we report a convergent and efficient synthesis of the C1-C9 fragment of the 7,8-O-isopropylidene protected iriomoteolide 3a derivative using (S)-(-)-citronellic acid as the starting material.…”

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confidence: 99%

Efficient Synthesis of the C1‐C9 Fragment of 7,8‐O‐Isopropylidene Protected Iriomoteolide 3a Derivative

Chang

2011

J Chinese Chemical Soc

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“…2 At the same time, we demonstrated the synthesis of the macrocyclic core of iriomoteolide-3a. 3 Later, the total synthesis of 7,8-O-isopropylidene iriomoteolide-3a was accomplished by Zhao and co-workers, 4 while synthesis of the C1-C9 fragment of 2 has been reported by Chang. 5 Figure 1 Structure of iriomoteolide-3a and its 7,8-O-isopropylidene derivative…”

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confidence: 99%

“…2 At the same time, we demonstrated the synthesis of the macrocyclic core of iriomoteolide-3a. 3 Later, the total synthesis of 7,8-O-isopropylidene iriomoteolide-3a was accomplished by Zhao and co-workers, 4 while synthesis of the C1-C9 fragment of 2 has been reported by Chang. 5 In continuation of our work on the synthesis of macrolides, including iriomoteolide-3a, 3,6 we initiated an alternative strategy towards various analogues of 1 for biological evaluation.…”

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confidence: 99%

“…3 Later, the total synthesis of 7,8-O-isopropylidene iriomoteolide-3a was accomplished by Zhao and co-workers, 4 while synthesis of the C1-C9 fragment of 2 has been reported by Chang. 5 In continuation of our work on the synthesis of macrolides, including iriomoteolide-3a, 3,6 we initiated an alternative strategy towards various analogues of 1 for biological evaluation. In this paper, we report the synthesis of the C10-C18 fragment, a key subunit of iriomoteolide-3a (1) having five stereocenters.…”

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Stereoselective Synthesis of the C10-C18 Fragment of Iriomoteolide-3a

Reddy¹,

Dharmapuri²

2013

Synthesis

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An efficient synthesis of the highly stereogenic centered C10-C18 fragment of iriomoteolide-3a has been accomplished. Key steps include Sharpless asymmetric dihydroxylation and epoxidation for generation of the desired stereocenters.In 2008, Tsuda and co-workers isolated a potent cytotoxic macrolide, iriomoteolide-3a (1, Figure 1), from a marine benthic dinoflagellate Amphidinium sp. (strain HYA024), which was monoclonally separated from sea sand collected off Iriomote Island, Japan. 1 Iriomoteolide-3a (1) is a 15-membered macrolide having a novel carbon framework comprising eight stereogenic centers including an allyl epoxide, four hydroxy groups and two methyl branches. Compound 1 represents a unique and novel 15-membered macrolide class compared to the other known 15-membered macrolides. Further, the initial in vitro screening showed that iriomoteolide-3a (1) and its 7,8-Oisopropylidene derivative 2 ( Figure 1) exhibit potent cytotoxicity against human B lymphocyte DG-75 and Raji cells in the low nanomolar range. The unique structural features of iriomoteolide-3a coupled with its potent cytotoxicity have attracted the attention of synthetic organic chemists. In 2009, Nevado and co-workers reported the first total synthesis of 1 along with biological evaluation of its analogues. 2 At the same time, we demonstrated the synthesis of the macrocyclic core of iriomoteolide-3a. 3 Later, the total synthesis of 7,8-O-isopropylidene iriomoteolide-3a was accomplished by Zhao and co-workers, 4 while synthesis of the C1-C9 fragment of 2 has been reported by Chang. 5 Figure 1 Structure of iriomoteolide-3a and its 7,8-O-isopropylidene derivativeIn continuation of our work on the synthesis of macrolides, including iriomoteolide-3a, 3,6 we initiated an alternative strategy towards various analogues of 1 for biological evaluation. In this paper, we report the synthesis of the C10-C18 fragment, a key subunit of iriomoteolide-3a (1) having five stereocenters. As shown in Scheme 1, our synthetic strategy for iriomoteolide-3a is convergent and involves a late-stage assembly of macrocyclic core 3 and side chain 4. The macrocycle 3 can be obtained from epoxy subunit 5 and sulfone 6 through a Julia-Kocienski olefination (C9-C10 bond formation) followed by Yamaguchi macrolactonization. The formation of the C9-C10 bond in all earlier approaches was accomplished using ring-closing metathesis. Scheme 1 Retrosynthetic analysis of iriomoteolide-3aThe synthesis of epoxy segment 5 (C10-C18 fragment) was carried out as shown in Scheme 2, starting from propane-1,3-diol (7). Monoprotection of diol 7 as the tert-butyldiphenylsilyl ether provided compound 8 in 98% yield. Swern oxidation of alcohol to aldehyde followed by Grignard reaction with vinylmagnesium bromide afforded the allyl alcohol 9 in 86% yield over two steps. 7 Treatment of 9 with triethyl orthoacetate in the presence of propanoic acid at 140°C for four hours gave the γ,δ-unsaturated ester 10 via ortho-Claisen rearrangement. 8 At this stage, the requisite chiral dihydroxy functionali...

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Olefin Ring‐Closing Metathesis

Yet

2016

Organic Reactions

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The olefin ring‐closing metathesis reaction catalyzed by ruthenium and molybdenum complexes has been employed in the syntheses of carbocycles, heterocycles, supramolecular compounds, and in tandem metathesis reactions. Chiral ruthenium and molybdenum catalysts have provided high enantiomeric and diastereomeric excesses in ring‐closing metathesis reactions. Many of the unsuccessful medium‐ and large‐sized ring formations which were unsuccessful by traditional methods, such as the intramolecular Wittig, Horner–Wadsworth–Emmons, and Julia–Kocienski reactions, can now be formed by olefin ring‐closing metathesis reactions. Ring‐closing metathesis has been a key step and sometimes the only successful method for the synthesis of numerous natural products and drug discovery targets. The objective of this chapter is to provide an updated, comprehensive coverage of the literature of the olefin ring‐closing metathesis reaction and related processes. Key mechanistic points are summarized.

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Synthesis of the Macrocyclic Core of Iriomoteolide 3a

Cited by 34 publications

References 33 publications

Efficient Synthesis of the C1‐C9 Fragment of 7,8‐O‐Isopropylidene Protected Iriomoteolide 3a Derivative

Efficient Synthesis of the C1‐C9 Fragment of 7,8‐O‐Isopropylidene Protected Iriomoteolide 3a Derivative

Stereoselective Synthesis of the C10-C18 Fragment of Iriomoteolide-3a

Olefin Ring‐Closing Metathesis

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