Novel, enantioselective lactone construction. First synthesis of methylenolactocin, antitumor antibiotic from Penicillium sp

Enantioselective Butenolide Preparation for Straightforward Asymmetric Syntheses of γ‐Lactones – Paraconic Acids, Avenaciolide, and Hydroxylated Eleutherol

“…A Japanese group had described the trans ‐addition of the related reagent Li–C(SPh) 3 to enantiopure butenolide S ‐ 20i 33. Like their (PhS) 3 C analogue33 of our (MeS) 3 C‐containing lactones R ‐ and S ‐ 21i and ‐ 21n , our compounds released the underlying HO 2 C‐substituted lactones upon Hg II ‐ and Lewis acid‐assisted hydrolysis (→ 91–94 % 22 ).α‐Activation of 22 by Stiles’ reagent, followed by aminomethylation/in situ fragmentation – as published for(–)‐ 13 34 and (–)‐ 14 30a – provided the target structures(+)‐ and (–)‐ 13 and ‐ 14 in 64–72 % yields 35…”

“…in DMF, 135–140 °C, 70 h; isolation of the crude product; (ii) crude product from previous reaction, HOAc/NaOAc/formalin (= 35–40 % aq. solution of formaldehyde)/ N ‐methylaniline (excess; 4:0.03:3:1), room temp., 2 h; 67 % (+)‐ 13 , 72 % (+)‐ 14 [enantiomeric series: analogously → 64 % (–)‐ 13 (ref 34. 66 %), 68 % (–)‐ 14 (ref 30a…”

“…Extraction with t BuOMe (3 × 20 mL), washing of the combined organic phases with brine (10 mL), drying over MgSO 4 , and removal of the solvent in vacuo followed by flash chromatography (4 cm, CHCl 3 /EtOAc/HOAc, 90:8:2, #8–19) yielded (–)‐ 13 (262 mg, 64 %) as a colorless solid (m.p. 83–84 °C, ref 34…”

Enzymatic Resolution of α‐Methyleneparaconic Acids and Evaluation of their Biological Activity

“…mp 82–83 °C; [α] D 32 = –8.5 ( c =0.31 in methanol),[α] D 29 = –11.6 ( c =0.31 in chloroform); Lit . [α] D 25 = –6.77 ( c =0.52 in methanol); Lit …”

Evolution of Strategies in Paraconic Acids Synthesis

“…Further, hydroxy elimination via mesylate gave the butenolide derivative 14 , which on catalytic hydrogenation furnished 15 a as syn / anti ‐diastereomer mixture (dr 4.3 : 1). Further, DBU mediated isomerization gave 15 b as a diastereomeric mixture ( anti/syn =3.5 : 1) in almost quantitaive yield. With 15 a and 15 b in hand, the synthesis of (+)‐methylenolactocin and (+)‐phaseolinic acid could be achieved via reported procedure .…”