Elsevier

Tetrahedron: Asymmetry

Volume 23, Issue 9, 15 May 2012, Pages 659-661
Tetrahedron: Asymmetry

A simple and efficient synthesis of goniothalesdiol A

https://doi.org/10.1016/j.tetasy.2012.05.002Get rights and content

Abstract

A concise, simple, and efficient stereoselective total synthesis of goniothalesdiol A starting from commercially available 2-deoxy-d-ribose is described herein using a stereocontrolled Grignard reaction, olefin cross-metathesis, and oxy-Michael addition reactions as the key steps.

Introduction

In recent years, the synthesis of substituted tetrahydropyrans has gained significant interest due to their potent biological properties. Tetrahydropyrans containing substituents at the 2- and 6-positions on the ring are observed in a large number of biologically important natural products. A few examples which come under this class include phorboxazole,1, 1(a) ratjadone,1b lasnolide,1c leucascandrolide,1d scytoohycins,1e soranicin-A,1f swinholides,1g laulimalide,1h and zamponolide.1i The two major types of bioactive compounds styryl lactones2 and acetogenins3 can be isolated from Goniothalamus species belonging to the annonaceae family. Recently goniothalesdiol A 1 and goniothalesacetate 2 (Fig. 1) were isolated from the stems of a southern Taiwan tree Goniothalamus amuyon. Goniothalesdiol A has been shown to possess a 2,3,4,6-tetrasubstituted pyran ring. The structure and relative configuration of 1 were determined on the basis of NMR spectroscopy and the absolute configuration was predicted by biosynthesis.4 Previously five syntheses have been reported, one based on a Sharpless kinetic resolution; the second synthesis based on a cross metathesis using Grubb’s second generation catalyst; a third involves a chiron approach; the fourth is based on a Prins cyclization and last one is using tandem aminoxylation–allylation reaction.5 Among those, She et al. achieved the asymmetric total synthesis of goniothalesdiol A in six steps with an overall yield of 30%.5 We have achieved a concise, simple, and efficient total synthesis of goniothalesdiol A in six steps and with 31% overall yield.

According to our retro-synthetic analysis, the construction of the tetrahydropyran ring of goniothalesdiol A would arise from the key intermediate hydroxyl ester 3 by intramolecular oxy-Michael addition which can be manipulated further by acetonide deprotection to give the target compound goniothalesdiol A. Ester 3 can in turn be obtained by olefin cross-metathesis of 4 with methyl acrylate. Olefinic alcohol 4 was synthesized from commercially available 2-deoxy-d-ribose involving a chiral pool approach using selective acetonide protection, one carbon homologation by a Wittig reaction and stereocontrolled Grignard reaction with phenyl magnesium bromide (Scheme 1).

Section snippets

Results and discussion

Initially, the synthesis began with the isopropylidine formation at the secondary hydroxyl groups at C3 and C4 of 2-deoxy-d-ribose 6 with 2,2-dimethoxy propane in the presence of a catalytic amount of PTSA to give compound 5.6 One carbon homologation using a Wittig protocol on lactol 5 with methyltriphenylphosphonium iodide in the presence of KHMDS yielded olefenic alcohol 7.7 The primary alcohol in the resultant product 7 was oxidized to the aldehyde by a Swern oxidation and the crude aldehyde

Conclusion

In conclusion, we have achieved a simple, versatile, and efficient stereoselective total synthesis of goniothalesdiol A in six steps with 31% overall yield starting from the 2-deoxy-d-ribose. The key reactions involved are the stereocontrolled Grignard reaction, olefin cross-metathesis, and acid-catalyzed oxy-Michael addition.

General

The reactions were carried out under N2 in anhydrous solvents such as CH2Cl2, THF, and EtOAc. THF used was freshly distilled over benzophenone prior to use. All reactions were monitored by TLC (silica-coated plates and visualized under UV light). Yields refer to isolated yields. Air-sensitive reagents were transferred by a syringe or a double-ended needle. 1H and 13C NMR spectra were recorded in CDCl3 solution on Brucker Avance 300 spectrometers. Chemical shifts are reported relative to TMS as

Acknowledgments

We are thankful to Dr. Reddy’s Laboratories Ltd for support and Maithili Life Sciences Pvt. Ltd for financial assistance.

References (10)

  • X. Geng et al.

    Org. Lett.

    (2004)
  • T. Kanger et al.

    Tetrahedron: Asymmetry.

    (1998)
  • P.A. Searle et al.

    J. Am. Chem. Soc.

    (1995)
    D. Schummer et al.

    Liebigs Ann.

    (1995)
    P.A. Horton et al.

    J. Am. Chem. Soc.

    (1994)
    M. D’Ambrosio et al.

    Helv. Chim. Acta

    (1996)
    R.E. Moore et al.

    Pure Appl. Chem.

    (1986)
    M. Ishibashi et al.

    J. Org. Chem.

    (1986)
    S. Carmely et al.

    Tetrahedron Lett.

    (1985)
    R. Jansen et al.

    Tetrahedron Lett.

    (1985)
    J. Tanaka et al.

    Chem. Pharm. Bull.

    (1990)
    J. Tanaka et al.

    Tetrahedron Lett.

    (1996)
  • A.A.E. El-Zayat et al.

    Tetrahedron Lett.

    (1987)
    T.W. Sam et al.

    Tetrahedron Lett.

    (1987)
    X.-P. Fang et al.

    J. Chem. Soc., Perkin Trans. 1

    (1990)
    X.-P. Fang et al.

    Tetrahedron

    (1991)
    X.-P. Fang et al.

    Tetrahedron

    (1993)
  • Z.-M. Gu et al.

    Tetrahedron Lett.

    (1994)
    X.-P. Fang et al.

    J. Nat. Prod.

    (1992)
There are more references available in the full text version of this article.

Cited by (6)

  • A three-step total synthesis of goniothalesdiol A using a one-pot Sharpless epoxidation/regioselective epoxide ring-opening

    2017, Tetrahedron Letters
    Citation Excerpt :

    Sharpless asymmetric epoxidation11 of allylic alcohol 3 using (+)-diethyl tartrate as a chiral ligand proceeded efficiently to produce epoxy alcohol 6 in 90% yield. Regioselective epoxide ring opening of epoxy alcohol 6 using hot water under the catalyst-free condition at 60 °C provided triol 2,12,9e which was then subjected to intramolecular oxa-Michael addition using the acid catalyst. At this stage, we anticipated that a desired THP product 1 would be obtained from triol 2 through an intramolecular 1,4-addition of the hydroxyl group present at the active benzylic position on the unsaturated ester.

  • The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2012

    2014, Coordination Chemistry Reviews
    Citation Excerpt :

    Classification is according to the “expendable” alkene using in the cross metathesis process. Several papers report on the cross metathesis of inexpensive low molecular weight α,β-unsaturated carbonyl compounds with other more precious alkenes, including cross metatheses of: (1) acrolein with an allylic alcohol derivative for total synthesis of stagonolide B [368], a homoallylic alcohol derivative for total synthesis of dictyostatin and analogs (synthesis also involves making a six-membered ring α,β-unsaturated lactone by RCM) [369], and silyl-protected 5-hexen-1-ol (104) [370]; (2) methacrolein with citronellal for total synthesis of fusarisetin A [371] and a vinyltetrahydropyran derivative (105) as part of an approach to zampanolide [372]; (3) homoallylic alcohol derivatives and either acrolein or methyl vinyl ketone [373]; (4) crotonaldehyde with a complex alkene-alcohol as part of a synthetic approach to lyngbyalosides [374] and with an alkene-carbamate for cermizine D total synthesis [375]; (5) methyl vinyl ketone and a homoallylic amine derivative for total synthesis of solenopsin and isosolenopsin [376]; (6) allylbenzenes and either methyl vinyl ketone or methyl acrylate (in the same pot as an aryl allylation reaction) [377]; (7) 1-hexen-3-one and an allylpyrrolidine derivative for total synthesis of poison frog alkaloid 239Q [378]; (8) a vinyl ketone and an allylic alcohol derivative for preparation of alpinoid C and analogs [379]; (9) various acrylate esters with 10-undecenenitrile [380], a C-allyl glycoside derivative [381], a C-allyl glycoside for total syntheses of herbicidin C and aureonuclemycin [382], a sulfinamine derivative (106) for the preparation of cocaine analogs [383], an allylic alcohol derived from proline for total synthesis of pumilliotoxin-251D [384], an allylic alcohol for total synthesis of pyrenophorol [385], homoallylic alcohol derivatives [386], a homoallylic alcohol derivative for total synthesis of cryptocaryolones [387], a homoallylic alcohol derivative for total synthesis of goniothalesdiol A [388], a homoallylic alcohol for synthesis of 39-oxobistramide K [389], a homoallylic alcohol derivative for total synthesis of hoprominols [390], a bis(allyl) biphenyl derivative (107) for preparation of dihydrobenzo[j]fluorenthene-12-one [391], a keto-diene in a double CM process for total synthesis of halichlorine [392], N-allylindoles [393], alkene-dihydropyridones (e.g. 108) [394], various monosubstituted alkenes linked to a dihydropyridone ring system [395], an N-allylamide derivative for preparation of falcipain-2 inhibitors [396], a vinyl-functionalized 2-oxazoline polymer [397], and plant-derived allylbenzene essential oils [398]; (10) acryloyl chloride or acrylamide and a complex alkene-alcohol derivative (e.g. 109) for total synthesis of palmyrolide A and its stereoisomers [399,400]; (11) phenyl vinyl ketone and a homoallylic alcohol derivative for total synthesis of crocacin C [401]; (12) cinnamic acid and ethylene [402]; and (13) an allylpyrazole and various electron deficient vinyl derivatives or styrene derivatives [403]. Several examples employing the cross metathesis of simple inexpensive low molecular weight functionalized allylic derivatives with more precious alkenes were reported in 2012, including: (1) allylic alcohols and allyl m-nitrophenyl ether [404]; (2) allyl acetate with a highly oxygenated homoallylic alcohol [405] and with an allylpyrrole derivative (110) for preparation of the macrocyclic portion of roseophilin [406]; (3) cis 1,4-diacetoxy-2-butene with homoallylic alcohols [407] and with an spirocyclic allyltetrahydrofuran derivative for total synthesis of spirastrellolide A methyl ester [408]; (4) 2-methyl-3-buten-2-ol and an allyl-cyclohexenone derivative for total synthesis of paspalinine [409]; (5) 3,3-diacetoxy-1-propene and an alkene-alcohol for synthesis of an amphidinolide N subunit [410]; (6) various monosubstituted alkenes with N-aryl-O-allyl carbamates [411]; (7) optically active 3-buten-2-ol and a vinyltetrahydrofuran derivative for total synthesis of isoaspinonene [412]; (8) allyl halides and various alkene-esters and alkene-amides [413]; (9) an N-allylamide derivative (111) and the silyl ether of 4-penten-1-ol for total synthesis of ajudazol B [414]; and (10) a vinyltetrahydrofuran derivative and an allylic alcohol derivative for total syntheses of orthodiffenes A and C [415].

  • Concise Synthesis of Goniothalesdiol A

    2022, Letters in Organic Chemistry
  • Alkene cross-metathesis reactions

    2021, Organic Reactions
View full text