85134-98-1Relevant articles and documents
Approach to the Core Structure of 15- epi -Exiguolide
Riefert, Alexander,Maier, Martin E.
, p. 3131 - 3145 (2018/08/17)
The synthesis of seco acid 41 of the macrolactone part of 15- epi -exiguolide, containing a bis-pyran subunit and a trans double bond, is described. Key features of the synthetic strategy include a Feringa-Minnaard asymmetric organocuprate addition to uns
Stereocontrolled synthesis of a Cn-Cn+7 building block ("eastern moiety") for the unnatural enantiomers of important polyol,polyene antibiotics based on a ring-closing metathesis and an aldol addition of a lactone enolate
Kamptmann, Sonja B.,Brueckner, Reinhard
supporting information, p. 6584 - 6600 (2013/11/06)
A stereocontrolled synthesis of epoxide 6, which represents the C n-Cn+7 or "eastern moiety" building block for the title compounds, has been realized in 19 steps. Our synthesis started from tetrabromoacetone 26 and afforded dibromotriene 33b in six steps. The latter was subjected to a ring-closing metathesis, which gave the dibromovinyl-substituted lactone 34 in high yield. A highly stereoselective conjugate addition/enolate aldolization sequence established the additional stereocenters with perfect selectivity. Epoxide 47b was reached in another eight steps, which included a C-SiMe2Pha€‰→a€‰C-OH oxidation in the presence of an acetal group. The final structure 6 was completed by hydrostannylation/brominolysis. A dibromovinyl-substituted unsaturated δ-lactone obtained by ring-closing metathesis underwent a highly diastereoselective silyl cuprate 1,4-addition/aldolization sequence. Tamao-Fleming oxidation transformed the silyl into a hydroxy group. Alkyne formation, hydrostannylation, and N-bromosuccinimidolysis converted the dibromovinyl into a trans-bromovinyl moiety. Copyright
Total synthesis of cytochalasin D: Total synthesis and full structural assignment of cytochalasin O
Merifield, Eric,Thomas, Eric J.
, p. 3269 - 3283 (2007/10/03)
A total synthesis of cytochalasin D 3 is reported in which the key step is an intramolecular Diels-Alder reaction used to close the 11-membered ring simultaneously introducing the required stereochemistry at four of the stereogenic centres, C(4), C(5), C(8) and C(9). The precursor 21 for the Diels-Alder reaction was prepared from the aldehyde 13 by condensation with the dienyl phosphonate 14 to give the triene 15 which, after conversion into the acyl imidazole 17, was used to acylate the pyrrolidinone 18. The unstable pyrrolinone 21 was then generated from the pyrrolidinone by phenylselenation-oxidative elimination and was cyclised by heating in toluene under high dilution conditions to give the macrocyclic triene 22 (25-30%). Selective functionalisation of the double-bonds in this triene was investigated with epoxidation being selective for the 17,18-double-bond and hydroxylation using osmium tetroxide taking place selectively at the 6,7-double-bond. For completion of the synthesis of cytochalasin D 3, the 6,7-diol 26 was converted into the exocyclic alkene 30 by protection and dehydration. Further hydroxylation using osmium tetroxide gave the diol 31 which was taken through to the enone 36 by protection followed by phenylselenation, N-debenzoylation and oxidative elimination. Reduction under Luche's conditions gave the alcohol 37 which was converted into the acetate 41 by acetylation followed by protecting group exchange. Selective deprotection of the vicinal diol and mild oxidation then gave the ketone 43. Final deprotection gave cytochalasin D 3 so completing the first total synthesis of this natural product. During the course of this work, the Diels-Alder adduct 22 was oxidised using an excess of osmium tetroxide to give the tetraol 28. After protection as its bis-acetonide 46, this was converted into the allylic acetate 51 using the chemistry developed during the synthesis of cytochalasin D 3. Selective hydrolysis of the 17,18-acetonide and oxidation under Swern conditions gave the hydroxyketone 53 which on deprotection gave cytochalasin O 54 so confirming the structure of this natural product. The Royal Society of Chemistry 1999.
