The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments.
Due to a combination of their promising anticancer properties, limited supply from the marine sponge source and their unprecedented molecular architecture, spirastrellolides represent attractive and challenging synthetic targets. A modular strategy for the synthesis of spirastrellolide A methyl este...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2012
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| _version_ | 1826295941003476992 |
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| author | Paterson, I Anderson, E Dalby, S Lim, J Maltas, P Loiseleur, O Genovino, J Moessner, C |
| author_facet | Paterson, I Anderson, E Dalby, S Lim, J Maltas, P Loiseleur, O Genovino, J Moessner, C |
| author_sort | Paterson, I |
| collection | OXFORD |
| description | Due to a combination of their promising anticancer properties, limited supply from the marine sponge source and their unprecedented molecular architecture, spirastrellolides represent attractive and challenging synthetic targets. A modular strategy for the synthesis of spirastrellolide A methyl ester, which allowed for the initial stereochemical uncertainties in the assigned structure was adopted, based on the envisaged sequential coupling of a series of suitably functionalised fragments; in this first paper, full details of the synthesis of these fragments are described. The pivotal C26-C40 DEF bis-spiroacetal was assembled by a double Sharpless asymmetric dihydroxylation/acetalisation cascade process on a linear diene intermediate, configuring the C31 and C35 acetal centres under suitably mild acidic conditions. A C1-C16 alkyne fragment was constructed by application of an oxy-Michael reaction to introduce the A-ring tetrahydropyran, a Sakurai allylation to install the C9 hydroxyl, and a 1,4-syn boron aldol/directed reduction sequence to establish the C11 and C13 stereocentres. Two different coupling strategies were investigated to elaborate the C26-C40 DEF fragment, involving either a C17-C25 sulfone or a C17-C24 vinyl iodide, each of which was prepared using an Evans glycolate aldol reaction. The remaining C43-C47 vinyl stannane fragment required for introduction of the unsaturated side chain was prepared from (R)-malic acid. |
| first_indexed | 2024-03-07T04:08:42Z |
| format | Journal article |
| id | oxford-uuid:c715d56a-6418-425d-9551-7d171ce305fb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:08:42Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:c715d56a-6418-425d-9551-7d171ce305fb2022-03-27T06:42:37ZThe stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c715d56a-6418-425d-9551-7d171ce305fbEnglishSymplectic Elements at Oxford2012Paterson, IAnderson, EDalby, SLim, JMaltas, PLoiseleur, OGenovino, JMoessner, CDue to a combination of their promising anticancer properties, limited supply from the marine sponge source and their unprecedented molecular architecture, spirastrellolides represent attractive and challenging synthetic targets. A modular strategy for the synthesis of spirastrellolide A methyl ester, which allowed for the initial stereochemical uncertainties in the assigned structure was adopted, based on the envisaged sequential coupling of a series of suitably functionalised fragments; in this first paper, full details of the synthesis of these fragments are described. The pivotal C26-C40 DEF bis-spiroacetal was assembled by a double Sharpless asymmetric dihydroxylation/acetalisation cascade process on a linear diene intermediate, configuring the C31 and C35 acetal centres under suitably mild acidic conditions. A C1-C16 alkyne fragment was constructed by application of an oxy-Michael reaction to introduce the A-ring tetrahydropyran, a Sakurai allylation to install the C9 hydroxyl, and a 1,4-syn boron aldol/directed reduction sequence to establish the C11 and C13 stereocentres. Two different coupling strategies were investigated to elaborate the C26-C40 DEF fragment, involving either a C17-C25 sulfone or a C17-C24 vinyl iodide, each of which was prepared using an Evans glycolate aldol reaction. The remaining C43-C47 vinyl stannane fragment required for introduction of the unsaturated side chain was prepared from (R)-malic acid. |
| spellingShingle | Paterson, I Anderson, E Dalby, S Lim, J Maltas, P Loiseleur, O Genovino, J Moessner, C The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments. |
| title | The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments. |
| title_full | The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments. |
| title_fullStr | The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments. |
| title_full_unstemmed | The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments. |
| title_short | The stereocontrolled total synthesis of spirastrellolide A methyl ester. Expedient construction of the key fragments. |
| title_sort | stereocontrolled total synthesis of spirastrellolide a methyl ester expedient construction of the key fragments |
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