Stereoselective total synthesis of (+)-anamarine via cross-metathesis protocol

Sabitha, Gowravaram; Reddy, Chintam Nagendra; Gopal, Peddabuddi; Yadav, J. S.

doi:10.1016/j.tetlet.2010.08.077

Cited by 32 publications

(13 citation statements)

References 52 publications

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“…The synthesis of aldehyde 7 started with readily available but-2-yn-1,4-diol (Scheme 5). Accordingly, but-2-yn-1,4diol was converted into the known allylic alcohol 15 as reported earlier, 12 by selective monobenzylation and partial reduction of the triple bond in a very good yield (90%). The alcohol 15 was subjected to Sharpless asymmetric epoxidation [(-)-DIPT, Ti(Oi-Pr) 4 , TBHP, -25°C, 24 h] to afford epoxy alcohol 16 in 76% yield.…”

Section: Synthetic Strategy For the C3-c11 Fragment (2)mentioning

confidence: 78%

Studies toward the Synthesis of Iejimalides A–D: Preparation of the C3–11 and C12–C24 Fragments

2013

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Abstract:The convergent synthesis of the C3-C11 and C12-C24 fragments of the iejimalides A-D is described. The C3-C11 fragment is obtained by a cross-metathesis reaction, while the C12-C24 fragment is derived from a Still-Gennari modified HornerWadsworth-Emmons olefination.Key words: iejimalides, macrolides, cross-metathesis, HornerWadsworth-Emmons, fragment synthesis Iejimalides A-D (1a-d) 1 are four novel polyene macrolides, isolated by Kobayashi and co-workers from the methanol extracts of the tunicate, Eudistoma cf. rigida, collected off Ie island, Okinawa province, Japan. Structurally, the iejimalides consist of a 24-membered polyene macrolide core structure containing five stereogenic centers, four conjugated diene units and an N-formyl-L-serine terminus (Figure 1). The iejimalides show potent growth inhibitory activity 2 against a range of human tumor cell lines, with iejimalide B being especially potent. According to the data disclosed by the National Cancer Institute (NCI), iejimalide A shows remarkable potency, with GI 50 values as low as 13 nM (MDA-MB-231/ATCC breast cancer cell line), and total growth inhibition (TGI) values as low as 40 nM (M14 melanoma cell line), whilst iejimalide B is cytostatic (GI 50 ) at <5 nm against 40 of the 60 standard human cancer cell lines tested. 3 In addition, the iejimalides show selective V-ATPase inhibition. 4 The overall structures of the iejimalides were first determined by Kobayashi in 1988, through degradation and NMR studies. 1a However, the specific stereochemistry of only one of the six stereogenic centers (i.e., C32, the others being located at C4, C9, C17, C22, and C23 ) was determined. After isolation of the iejimalides in relatively large amounts from Cystodytes sp., 5 published revised structures for the iejimalides, with complete determination of the absolute configurations at the six stereogenic centers. They also reported a change in the olefin geometry at C13 (Z rather than E), following extensive 2D NMR investigations, distance geometry calculations and degradation studies. 6 So far, three total syntheses 7 and two syntheses of fragments 8 have been reported. The distinctive biological properties of the iejimalides and their scarcity (0.0003-0.0006% of the tunicate wet weight) in Nature, combined with their unique and intriguing molecular architecture, renders these natural products attractive synthetic targets, which has prompted us to study the synthesis of these natural products. In this connection, we herein report our preliminary studies on the synthesis of the C3-C11 and C12-C24 fragments of iejimalides A-D. Scheme 1 outlines our retrosynthetic analysis of iejimalides A-D. The C3-C11 fragment 2 could be assembled by a cross-metathesis reaction between alkenes 4 and 5. The subunit 4 was envisioned to originate from but-3-yn-1-ol (homopropargylic alcohol), while synthon 5 could be derived from (S)-Roche ester. The C12-C24 fragment could arise from a Still-Gennari modified HornerWadsworth-Emmons olefination reaction between phosphonate 6 and ...

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Section: Synthetic Strategy For the C3-c11 Fragment (2)mentioning

confidence: 78%

Studies toward the Synthesis of Iejimalides A–D: Preparation of the C3–11 and C12–C24 Fragments

2013

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“…8 Herein, we report the stereoselective total synthesis of (À)-spicigerolide from chiral pool L-(+)-DET and homopropargyl alcohol, constructing a lactone ring via a Stille-Gennari reaction. So far, three syntheses 9 have been reported for the synthesis of (À)-spicigerolide based on an RCM strategy.…”

Section: Resultsmentioning

confidence: 99%

Stereoselective total synthesis of the cytotoxic lactone (−)-spicigerolide

Sabitha

Reddy

Raju

et al. 2011

Tetrahedron: Asymmetry

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“…Evaporation of the solvent and purification of the resulting residue by column chromatography using petroleum ether/EtOAc (95:05) as eluent furnished 17 (0.148 g) in 62% yield for three steps as colorless oil: [R] 24 D +38.9 (c 0.8, CHCl 3 ); IR (neat) 2932, 2888, 1647, 1198, 1074, 1031, 833 cm À1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7.39À7.22 (m, 5H), 5.80 (ddt, J = 17.0, 9.8, 7.0 Hz, 1H), 5.70 (dd, J = 15. 6,5.4 Hz,1H),5.65 (dd,J = 15.6,4.7 Hz,1H),5.07 (dd,J = 16.9,9.8 Hz,2H),4.74,4.58 (ABq,J = 6.7 Hz,2H),4.58,4.38 (ABq,J = 11.8 Hz,2H),4.23 (dd,J = 7.1,4.3 Hz,1H),4.07 (dd,J = 6.0,3.9 Hz, 1H), 3.97À3.85 (m,2H),3.82 (dq,J = 12.7,6.2 Hz,1H) 5,136.0,134.3,130.0,128.3,127.7,127.5,117.1,109.6,93.3,82.1,81.0,79.2,75.5,70.5,70.3,55.7,40.2,27.9,27.3,25.9,21.3,18.0,…”

Section: (+)-Anamarinementioning

confidence: 99%