Non-iterative asymmetric synthesis of C15 polyketide spiroketals

Kai Meilert, George Pettit, Pierre Vogel

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The 2,2′-methylenebis[furan] (1) was converted to 1-{(4R,6S))-6-[(2R)-2,4-dihydroxybutyl]-2,2-dimethyl-1,3-dioxan-4-yl}-3-[(2R,4R) -tetrahydro-4,6-dihydroxy-2H-pyran-2-yl)propan-2-one ((+)-18) and its (4S)-epimer (-)-19 with high stereo- and enantioselectivity (Schemes 1-3). Under acidic methanolysis, (+)-18 yielded a single spiroketal, (3R)-4-((1R,3S, 4′R,5R,6′S,7R)-3′,4′,5′,6′-tetrahydro- 4′-hydroxy-7-methoxyspiro[2,6-dioxabicyclo[3.3.1]nonane-3,2′-[2H] pyran]-6′-yl}butane-1,3-diol ((-)-20), in which both O-atoms at the spiro center reside in equatorial positions, this being due to the tricyclic nature of (-)-20 (methyl pyranoside formation). Compound (-)-19 was converted similarly into the (4′S)-epimeric tricyclic spiroketal (-)-21 that also adopts a similar (3S)-configuration and conformation. Spiroketals (-)-20, (-)-21 and analog (-)-23, i.e., (1R,3S,4′R,5R,6′R)-3′,4′,5′, 6′-tetrahydro-6′-[(2S)-2-hydroxybut-3-enyl]-7-methoxyspiro[2, 6-dioxabicyclo[3.3.1]-nonane-3,2′-[2H]pyran]-4′-ol, derived from (-)-20, were assayed for their cytotoxicity toward murine P388 lymphocytic leukemia and six human cancer cell lines. Only racemic (±)-21 showed evidence of cancer-cell-growth inhibition (P388, ED50: 6.9 μg/ml).

Original languageEnglish (US)
Pages (from-to)1493-1507
Number of pages15
JournalHelvetica Chimica Acta
Volume87
Issue number6
DOIs
StatePublished - 2004

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Pyrans
Polyketides
Stereoselectivity
nonanes
Enantioselectivity
Butane
Cell growth
Cytotoxicity
Conformations
cancer
Cells
Atoms
leukemias
furans
synthesis
butanes
cultured cells
Lymphoid Leukemia
analogs
Neoplasms

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Non-iterative asymmetric synthesis of C15 polyketide spiroketals. / Meilert, Kai; Pettit, George; Vogel, Pierre.

In: Helvetica Chimica Acta, Vol. 87, No. 6, 2004, p. 1493-1507.

Research output: Contribution to journalArticle

Meilert, Kai ; Pettit, George ; Vogel, Pierre. / Non-iterative asymmetric synthesis of C15 polyketide spiroketals. In: Helvetica Chimica Acta. 2004 ; Vol. 87, No. 6. pp. 1493-1507.
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abstract = "The 2,2′-methylenebis[furan] (1) was converted to 1-{(4R,6S))-6-[(2R)-2,4-dihydroxybutyl]-2,2-dimethyl-1,3-dioxan-4-yl}-3-[(2R,4R) -tetrahydro-4,6-dihydroxy-2H-pyran-2-yl)propan-2-one ((+)-18) and its (4S)-epimer (-)-19 with high stereo- and enantioselectivity (Schemes 1-3). Under acidic methanolysis, (+)-18 yielded a single spiroketal, (3R)-4-((1R,3S, 4′R,5R,6′S,7R)-3′,4′,5′,6′-tetrahydro- 4′-hydroxy-7-methoxyspiro[2,6-dioxabicyclo[3.3.1]nonane-3,2′-[2H] pyran]-6′-yl}butane-1,3-diol ((-)-20), in which both O-atoms at the spiro center reside in equatorial positions, this being due to the tricyclic nature of (-)-20 (methyl pyranoside formation). Compound (-)-19 was converted similarly into the (4′S)-epimeric tricyclic spiroketal (-)-21 that also adopts a similar (3S)-configuration and conformation. Spiroketals (-)-20, (-)-21 and analog (-)-23, i.e., (1R,3S,4′R,5R,6′R)-3′,4′,5′, 6′-tetrahydro-6′-[(2S)-2-hydroxybut-3-enyl]-7-methoxyspiro[2, 6-dioxabicyclo[3.3.1]-nonane-3,2′-[2H]pyran]-4′-ol, derived from (-)-20, were assayed for their cytotoxicity toward murine P388 lymphocytic leukemia and six human cancer cell lines. Only racemic (±)-21 showed evidence of cancer-cell-growth inhibition (P388, ED50: 6.9 μg/ml).",
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T1 - Non-iterative asymmetric synthesis of C15 polyketide spiroketals

AU - Meilert, Kai

AU - Pettit, George

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N2 - The 2,2′-methylenebis[furan] (1) was converted to 1-{(4R,6S))-6-[(2R)-2,4-dihydroxybutyl]-2,2-dimethyl-1,3-dioxan-4-yl}-3-[(2R,4R) -tetrahydro-4,6-dihydroxy-2H-pyran-2-yl)propan-2-one ((+)-18) and its (4S)-epimer (-)-19 with high stereo- and enantioselectivity (Schemes 1-3). Under acidic methanolysis, (+)-18 yielded a single spiroketal, (3R)-4-((1R,3S, 4′R,5R,6′S,7R)-3′,4′,5′,6′-tetrahydro- 4′-hydroxy-7-methoxyspiro[2,6-dioxabicyclo[3.3.1]nonane-3,2′-[2H] pyran]-6′-yl}butane-1,3-diol ((-)-20), in which both O-atoms at the spiro center reside in equatorial positions, this being due to the tricyclic nature of (-)-20 (methyl pyranoside formation). Compound (-)-19 was converted similarly into the (4′S)-epimeric tricyclic spiroketal (-)-21 that also adopts a similar (3S)-configuration and conformation. Spiroketals (-)-20, (-)-21 and analog (-)-23, i.e., (1R,3S,4′R,5R,6′R)-3′,4′,5′, 6′-tetrahydro-6′-[(2S)-2-hydroxybut-3-enyl]-7-methoxyspiro[2, 6-dioxabicyclo[3.3.1]-nonane-3,2′-[2H]pyran]-4′-ol, derived from (-)-20, were assayed for their cytotoxicity toward murine P388 lymphocytic leukemia and six human cancer cell lines. Only racemic (±)-21 showed evidence of cancer-cell-growth inhibition (P388, ED50: 6.9 μg/ml).

AB - The 2,2′-methylenebis[furan] (1) was converted to 1-{(4R,6S))-6-[(2R)-2,4-dihydroxybutyl]-2,2-dimethyl-1,3-dioxan-4-yl}-3-[(2R,4R) -tetrahydro-4,6-dihydroxy-2H-pyran-2-yl)propan-2-one ((+)-18) and its (4S)-epimer (-)-19 with high stereo- and enantioselectivity (Schemes 1-3). Under acidic methanolysis, (+)-18 yielded a single spiroketal, (3R)-4-((1R,3S, 4′R,5R,6′S,7R)-3′,4′,5′,6′-tetrahydro- 4′-hydroxy-7-methoxyspiro[2,6-dioxabicyclo[3.3.1]nonane-3,2′-[2H] pyran]-6′-yl}butane-1,3-diol ((-)-20), in which both O-atoms at the spiro center reside in equatorial positions, this being due to the tricyclic nature of (-)-20 (methyl pyranoside formation). Compound (-)-19 was converted similarly into the (4′S)-epimeric tricyclic spiroketal (-)-21 that also adopts a similar (3S)-configuration and conformation. Spiroketals (-)-20, (-)-21 and analog (-)-23, i.e., (1R,3S,4′R,5R,6′R)-3′,4′,5′, 6′-tetrahydro-6′-[(2S)-2-hydroxybut-3-enyl]-7-methoxyspiro[2, 6-dioxabicyclo[3.3.1]-nonane-3,2′-[2H]pyran]-4′-ol, derived from (-)-20, were assayed for their cytotoxicity toward murine P388 lymphocytic leukemia and six human cancer cell lines. Only racemic (±)-21 showed evidence of cancer-cell-growth inhibition (P388, ED50: 6.9 μg/ml).

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