No abstract

Famoxadone (3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione), is a new agricultural fungicide recently commercialized by DuPont under the trade name Famoxate. Famoxadone is a member of a new class of oxazolidinone fungicides that demonstrate excellent control of plant pathogens in the Ascomycete, Basidiomycete, and Oomycete classes that infect grapes, cereals, tomatoes, potatoes and other crops. DuPont's entry into the oxazolidinone area resulted from the procurement of 5-methyl-5-phenyl-3-phenylamino-2-thioxo-4-oxazolidinone (1) from Professor Detlef Geffken, then at the University of Bonn. An extensive analog program was initiated immediately after the fungicidal activity of 1 was discovered through routine greenhouse testing. The discovery program in the oxazolidinone area eventually culminated in the advancement of famoxadone to commercial development in the early 1990s. The synthesis of various oxazolidinone ring systems and the development of the structure-activity relationships that led to the discovery of famoxadone are described.

An efficient enantioselective synthesis of benzyl (1S,2R,4R)-4-(tert-butoxycarbonylamino)-2-(hydroxymethyl)cyclohexylcarbamate 2, an essential intermediate for a series of potent CCR2 antagonists, is described. The key step in the sequence is an iodolactamization to yield the highly functionalized (1R,2S,4S,5S)-tert-butyl 2-(benzyloxycarbonylamino)-4-iodo-7-oxo-6-azabicyclo[3.2.1]octane-6-carboxylate 11. An examination of the reaction mechanism within the 2-step iodolactamization sequence led to the discovery of a single-pot transformation of increased efficiency.

Concise total syntheses of the Amaryllidaceae alkaloids (f)-crinine (1) and (*)-buphanisine (2) have been achieved. The overall strategy features the novel application of a general protocol for elaboration of a quaternary carbon at a carbonyl center to effect the facile construction of the key intermediate 4,4-disubstituted cyclohexenone 12 from the monoprotected 1,4-dione 8. Transformation of 12 into dienone 14 was readily accomplished by sequential a'-bromination and dehydrobromination; subsequent removal of the N-(ally1oxy)carbonyl protecting group was accompanied by spontaneous cyclization to give exclusively the cis-hydroindolenone 15. Hydride reduction of 15 afforded a mixture of epimeric allylic alcohols 25 and 26; inversion of the hydroxyl function in 26 via the mesylate 27 to give the requisite 25 proceeded without event. N-Debenzylation of 25 followed by insertion of the bridging methylene group onto 30 by a Pictet-Spengler reaction afforded (A)-crinine (1). Alternatively, treatment of a mixture of 25 and 26 with methanesulfonyl chloride followed by methanolysis of the resulting epimeric mesylates afforded 28 which was converted into (f)-buphanisine (2) by sequential N-debenzylation and Pictet-Spengler cyclization. An attempt to effect the highly diastereoselective formation of hydroindolenone 23 from enantiomerically pure 22 was unsuccessful.(Ally1oxy)methyl-substituted N,"-dibenzyldiaza-l8-crown-6 was prepared by five different processes. A simple Okahara ring closure of an (ally1oxy)methyl-substituted diazahexaethylene glycol proved to be the most convenient method. The corresponding N,N'-dihexyl-and N,N'-diethyldiaza-lB-crown-6 compounds were also prepared. These (ally1oxy)methyl-substituted crown compounds were covalently bonded to silica gel by first forming a diethoxymethylsilane containing the crown and coating this silane material onto silica gel and heating. The new silica gel-crown material separated Hg(I1) ions from Cd(I1) and Zn(I1) when an aqueous solution of p H 2 containing equal concentrations of all three cation nitrates was passed over it.

The first total synthesis of (-)-calicoferol B (III) is described. The cyclozirconation product I, prepared in enantiomerically pure form, was converted into the CD ring chiron II. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of III. The first total synthesis of (-)-calicoferol B (1) is described. The cyclozirconation product 8, prepared in enantiomerically pure form, was converted into the CD ring chiron 6. This was coupled with the aromatic A-ring, and then the side chain was constructed with control of relative and absolute configuration to complete the total synthesis of 1.