Total synthesis of enantiopure 1,3-dimethylpyranonaphthoquinones including ventiloquinones E, G, L and eleutherin.

A new synthetic approach to enantiopure pyranonaphthoquinones is described. (S)-Mellein 10, prepared in 6 steps from (S)-propylene oxide 16, is converted stereospecifically to the (1R,3S)-dimethylpyran 15. The pyran 15 is then converted to the benzoquinone 14, which undergoes regiospecific Diels-Alder reactions with a variety of oxygenated butadienes to give pyranonaphthoquinones including ventiloquinones E, G, L, eleutherin and ent-deoxyquinone A.

[1]  E. L. Patterson,et al.  Isolation of the optical antipode of mellein from an unidentified fungus , 1966, Experientia.

[2]  I. Green,et al.  The synthesis of ventiloquinone L, the monomer of cardinalin 3. , 2004, Organic & biomolecular chemistry.

[3]  M. Gill,et al.  Synthesis of pyran and pyranone natural products. , 2004, Molecules.

[4]  R. Giles.  The Diastereoselective Syntheses of Enantiopure Benzo- and Naphtho-pyrans Related to the Aphid Insect Pigments , 2004 .

[5]  M. Gill,et al.  Pigments of fungi. Part 68. Synthesis and absolute configuration of thysanone , 2002 .

[6]  K. Bastow,et al.  Novel mechanisms of DNA topoisomerase II inhibition by pyranonaphthoquinone derivatives—eleutherin, α lapachone, and β lapachone∗ , 2000 .

[7]  M. Brimble,et al.  Synthetic Strategies Towards Pyranonaphthoquinone Antibiotics , 2000 .

[8]  M. Brimble,et al.  Pyranonaphthoquinone antibiotics--isolation, structure and biological activity. , 1999, Natural product reports.

[9]  M. Gill,et al.  The first stereospecific approach to both enantiomers of mellein , 1997 .

[10]  D. Cameron,et al.  Synthesis of Ventilagone , 1992 .

[11]  R. H. Thomson,et al.  Benzisochromanquinones fromVentilago goughii , 1991 .

[12]  G. Kraus,et al.  Synthesis of deoxyfrenolicin and nanaomycin A , 1987 .

[13]  G. Kraus,et al.  Reduction of cyclic hemiacetals. The synthesis of demethoxyeleutherin and nanaomycin A , 1986 .

[14]  B. Rao,et al.  Benzisochromanquinones in ventilago species , 1985 .

[15]  G. Pietersz,et al.  Colouring matters of the Aphidoidea. XLV. Synthesis of (±)-deoxyquinone A dimethyl ether and its epimer (±)-cis-7,9-Dimethoxy-1,3-dimethyl-3,4,5,10-tetrahydro-1 H-naphtho[2,3-c]pyran-5,10-dione [(±)-7-Methoxyeleutherin] , 1982 .

[16]  H. W. Moore.  Bioactivation as a model for drug design bioreductive alkylation. , 1977, Science.

[17]  R. Smith,et al.  Toxins causing noninflammatory paralytic neuronopathy. Isolation and structure elucidation. , 1975, Journal of the American Chemical Society.

[18]  D. Cameron,et al.  Colouring matters of the Aphididae. XXXIX. Deoxyprotoaphin , 1972 .

[19]  Richard E. Moore,et al.  Electronic spectra of substituted naphthoquinones , 1968 .

[20]  J. Bowie,et al.  Colouring matters of the Aphididae. Part XXXIV. Rhodo- and xantho-dactynaphins , 1967 .

[21]  Richard E. Moore,et al.  Nuclear Magnetic Resonance Spectra of Substituted Naphthoquinones. Influence of Substituents on Tautomerism, Anisotropy, and Stereochemistry in the Naphthazarin System1 , 1966 .

[22]  D. Kingston,et al.  10. Colouring matters of the Aphididæ. Part XVII. The structure and absolute stereochemistry of the protoaphins , 1964 .

[23]  H. Schmid,et al.  Über die Konfiguration der Eleutherine‐Chinone (Inhaltsstoffe aus Eleutherine bulbosa (Mill.) Urb. V.) , 1951 .

[24]  H. Schmid,et al.  Über die Konstitution des Eleutherins. (Inhaltsstoffe aus Eleutherine bulbosa (Mill.) Urb. III) , 1950 .