Akaterpin, a novel bioactive triterpene from the marine sponge Callyspongia sp.

Fukami, Akiko; Ikeda, Yoko; Kondo, Shinichi; Naganawa, Hiroshi; Takeuchi, Tomio; Furuya, Shigeki; Hirabayashi, Yoshio; Shimoike, Kazuyuki; Hosaka, S.; Watanabe, Yoko; Umezawa, Kazuo

doi:10.1016/s0040-4039(97)00016-6

Cited by 37 publications

(38 citation statements)

References 5 publications

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“…This asymmetric and exo -selective Diels–Alder reaction sets the stage for the synthesis of other diterpenes bearing the halimane skeleton as present in tuberculosinol (i.e., akaterpin, 34 siphonodictyal D, 35 neopolypodatetraene A, 23 cacospongionolide F, 36 11 R *-acetoxyhalima-5,13 E -dien-15-oic acid, 37 and mamanuthaquinone 38 ).…”

Section: Discussionmentioning

confidence: 99%

Stereoselective Synthesis of 1-Tuberculosinyl Adenosine; a Virulence Factor of Mycobacterium tuberculosis

et al. 2016

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Despite its status as one of the world’s most prevalent and deadly bacterial pathogens, Mycobacterium tuberculosis (Mtb) infection is not routinely diagnosed by rapid and highly reliable tests. A program to discover Mtb-specific biomarkers recently identified two natural compounds, 1-tuberculosinyl adenosine (1-TbAd) and N6-tuberculosinyl adenosine (N6-TbAd). Based on their association with virulence, the lack of similar compounds in nature, the presence of multiple stereocenters, and the need for abundant products to develop diagnostic tests, synthesis of these compounds was considered to be of high value but challenging. Here, a multigram-scale stereoselective synthesis of 1-TbAd and N6-TbAd is described. As a key-step, a chiral auxiliary-mediated Diels–Alder cycloaddition was developed, introducing the three stereocenters with a high exo endo ratio (10:1) and excellent enantioselectivity (>98% ee). This constitutes the first entry into the stereoselective synthesis of diterpenes with the halimane skeleton. Computational studies explain the observed stereochemical outcome.

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Section: Discussionmentioning

confidence: 99%

Stereoselective Synthesis of 1-Tuberculosinyl Adenosine; a Virulence Factor of Mycobacterium tuberculosis

et al. 2016

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“…Absorbance frequencies are recorded in reciprocal centimeters (cm Melting points were recorded on Yanaco MP-3S. 1 H-NMR spectra were acquired at 400 MHz on a JEOL JNM-LD400 spectrometer or 500 MHz on a JNM-ECP500 spectrometer. Chemical shifts are reported in delta (δ) units in parts per million (ppm) relative to the singlet (7.26 ppm) for chloroform-d or the quartet (3.30 ppm) for methanol-d 4 .…”

Section: Methodsmentioning

confidence: 99%

“…Umezawa and co-workers originally isolated akaterpin (1) from the marine sponge Callyspongia sp. as an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC).…”

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confidence: 99%

Determination of the Absolute Structure of (+)-Akaterpin

Hosoi

Kawai

Hagiwara

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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We describe the total synthesis and structural determination of ( )-akaterpin (1), an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC). The key features of the synthetic strategy include the resolution of β,γ-unsaturated ketone ( )-2a with chiral sulfoximine 6. The absolute stereochemistry was determined by comparison of the specific optical rotation data of ( )-1 and ( )-1 with that of natural akaterpin.Key words total synthesis; absolute stereochemistry; optical resolution Umezawa and co-workers originally isolated akaterpin (1) from the marine sponge Callyspongia sp. as an inhibitor of phosphatidylinositol-specific phospholipase C (PI-PLC).1) PI-PLC triggers phosphatidylinositol turnover by hydrolyzing phosphatidylinositol 4,5-bisphosphate (PIP 2 ) into diacylglycerol (DG) and 1,4,5-trisphosphate (IP 3 ). Thus, a specific PI-PLC inhibitor is considered a promising anti-tumor candidate and a valuable tool for the investigation of signal transduction. 2,3)Until recently the precise structure of akaterpin had not been determined because of difficulties in isolating this compound from the natural source. We have been investigating a synthetic study of akaterpin and recently reported the relative stereochemistry of the compound by synthesizing possible isomers in racemic form and comparing the corresponding spectral data with those of the authentic natural product.4) Herein we describe the determination of the absolute stereochemistry of (+)-akaterpin. Our approach was to synthesize optically active akaterpin by resolution of the key intermediate in the racemic synthesis. We reasoned that β,γ-unsaturated ketone 2a was suitable for this purpose. Having resolved the key intermediate 2a, each enantiomer was then separately transformed to akaterpin following the same synthetic procedure as used for the racemate.In this regard, we previously reported the successful resolution of methyl-protected 2b by using chiral sulfoximine 6, which was developed by Johnson. 5,6) The absolute stereochemistry of both enantiomers of 2b was then established by X-ray crystallographic analysis of 7b and 9b 7) (Chart 2). We envisaged the resolution of benzyl-protected 2a, the synthetic intermediate of racemic akaterpin, 8) would also be possible as 2b. Thus, both enantiomers of akaterpin could be synthesized

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“…having disulfated hydroquinone moiety, is an inhibitor of phosphatidylinositol-specific phospholipase C with an IC 50 value of 0.5 μg/mL. It also inhibits neutral sphingomyelinase weakly with an IC 50 of 30 μg/mL [198]. Three new disulfated meroterpenoids, ilhabelanol ( 299 ), ilhabrene ( 300 ), both with unprecedented meroterpenoid carbon skeletons, and isoakaterpin ( 301 ), have been isolated from extracts of the same sponge (Figure 22).…”

Section: Meroterpenes From Spongesmentioning

confidence: 99%

Meroterpenes from Marine Invertebrates: Structures, Occurrence, and Ecological Implications

et al. 2013

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Meroterpenes are widely distributed among marine organisms; they are particularly abundant within brown algae, but other important sources include microorganisms and invertebrates. In the present review the structures and bioactivities of meroterpenes from marine invertebrates, mainly sponges and tunicates, are summarized. More than 300 molecules, often complex and with unique skeletons originating from intra- and inter-molecular cyclizations, and/or rearrangements, are illustrated. The reported syntheses are mentioned. The issue of a potential microbial link to their biosynthesis is also shortly outlined.

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Akaterpin, a novel bioactive triterpene from the marine sponge Callyspongia sp.

Cited by 37 publications

References 5 publications

Stereoselective Synthesis of 1-Tuberculosinyl Adenosine; a Virulence Factor of Mycobacterium tuberculosis

Stereoselective Synthesis of 1-Tuberculosinyl Adenosine; a Virulence Factor of Mycobacterium tuberculosis

Determination of the Absolute Structure of (+)-Akaterpin

Meroterpenes from Marine Invertebrates: Structures, Occurrence, and Ecological Implications

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