Total Synthesis of 10-Deoxymethynolide, the Aglycon of the Macrolide Antibiotic 10-Deoxymethymycin

Abstract

A short and efficient total synthesis of 10-deoxymethynolide (2c), the aglycon of 10-deoxymethymycin (1c), has been accomplished in 16 steps and 12% overall yield from (S)-3-O-p-toluenesulfonyl-3-hydroxy-2-methylpropanal (15c). The synthesis features an expeditious preparation of (+)-5a, a synthetic equivalent of the Prelog−Djerassi lactonic acid, and the construction of a 12-membered lactone through an intramolecular Nozaki−Hiyama−Kishi coupling reaction.

Total Synthesis of Trioxacarcin DC‐45‐A2

“…Intermediate 21 was advanced to the key cyclization precursor 6 , as summarized in Scheme . Thus, Stille coupling of aryl iodide 21 with stannane 8 10 proceeded in the presence of CuTC and catalytic amounts of Pd(PPh 3 ) 4 11 to afford allylic alcohol 22 (74 % yield), whose oxidation with TEMPO and PIDA gave aldehyde 23 (89 % yield). Jørgensen asymmetric epoxidation of α,β‐unsaturated aldehyde 23 ( 24 cat., urea⋅H 2 O 2 )12 led to epoxyaldehyde 25 , which was subjected without purification to Baylis–Hillman reaction with enone 7 13 (DABCO, 4‐nitrophenol) to give labile hydroxyepoxide 26 .…”

Total Synthesis of Trioxacarcin DC‐45‐A2

“…Thus, Stille coupling of aryl iodide 21 with stannane 8 [10] proceeded in the presence of CuTC and catalytic amounts of Pd(PPh 3 ) 4 [11] to afford allylic alcohol 22 (74 % yield), whose oxidation with TEMPO and PIDA gave aldehyde 23 (89 % yield). Thus, Stille coupling of aryl iodide 21 with stannane 8 [10] proceeded in the presence of CuTC and catalytic amounts of Pd(PPh 3 ) 4 [11] to afford allylic alcohol 22 (74 % yield), whose oxidation with TEMPO and PIDA gave aldehyde 23 (89 % yield).…”

“…Intermediate 21 was advanced to the key cyclization precursor 6, as summarized in Scheme 3. Thus, Stille coupling of aryl iodide 21 with stannane 8 [10] proceeded in the presence of CuTC and catalytic amounts of Pd(PPh 3 ) 4 [11] to afford allylic alcohol 22 (74 % yield), whose oxidation with TEMPO and PIDA gave aldehyde 23 (89 % yield). Jørgensen asymmetric epoxidation of a,b-unsaturated aldehyde 23 (24 cat., urea·H 2 O 2 ) [12] led to epoxyaldehyde 25, which was subjected without purification to Baylis-Hillman reaction with enone 7 [13] (DABCO, 4-nitrophenol) to give labile hydroxyepoxide 26.…”

Desmethyl Macrolides: Synthesis and Evaluation of 4,8,10-Tridesmethyl Cethromycin

“…xx, xxi, xxii To this end, the primary TBS ether of 16 was selectively removed under acidic conditions in 92% yield. Oxidation of alcohol 17 with the Dess–Martin periodinane (DMP) buffered with solid NaHCO 3 proceeded smoothly to furnish macrocyclization precursor 18 in 85% yield.…”