Jerauld S. Skotnicki

Synthesis of secorapamycin esters and amides

Abstract Secorapamycin acid has been converted to a variety of functionalized esters and amides. Sequential retroaldol / realdol reaction of a secorapamycin amide provided a truncated analog.

Ring expanded rapamycin derivatives

Abstract Two ring expanded rapamycin derivatives were synthesized from secorapamycin acid via sequential conjugate addition and high dilution macrolactone (lactam) formation.

Base catalyzed degradations of rapamycin

Abstract The base catalyzed degradation of rapamycin was re-examined and a sequence of steps involving β-elimination, retro-aldol cleavage and benzilic acid rearrangement occur leading to several new products.

Synthesis of analogues of folic acid, aminopterin and methotrexate as antitumour agents.

Publisher Summary This chapter discusses the syntheses of folic acid, aminopterin, and methotrexate analogs in which an intact L-glutamic acid side-chain is present while simultaneously varying the pteridine ring moiety, the C-9, N- 10 bridge and/or the benzoyl group. Several analogs of folic acid are known in which the only remaining structural feature of the folic acid molecule is the p-aminobenzoylglutamic acid moiety. Biological results are discussed in those cases where the analog has significant activity in tumor systems relative to methotrexate (MTX) or aminopterin (AP). Of the many classes of deazaFA derivatives investigated, none has received more attention or resulted in more promising candidate drugs than 5,8-dideaza (quinazoline) analogs. Methylation of folic acid (FA) with a 4-molar excess of methyl iodide gave a low yield of the tetramethyl derivative. A Dimroth rearrangement brought about by base at room temperature then gave hydrolysis of the methyl esters having taken place under the conditions of the rearrangement.

Improved Synthesis of 1,5-Bis(Dimethylamino)-1,4-Pentadien-3-One

Abstract 1,5-Bis (dimethylamino)-1,4-pentadien-3-one is conveniently prepared in quantitative yield by reaction of 1,3-acetone-dicarboxylic acid with dimethylformamide dimethylacetal.