Total Syntheses of Lactonamycin and Lactonamycin Z with Late‐Stage A‐Ring Formation and Glycosylation

Abstract

Scheme 1. Lactonamycin (1), lactonamycin Z (2), lactonamycinone (3), and model BCDEF aglycon (AE)-4. Scheme 2. Intermediates 5 and 6 synthesized by other research groups.Scheme 6. Synthesis of (AE)-lactonamycinone ((AE)-3) through a Bischler-Napieralski-type cyclization. a) PdCl 2 , 1,4-benzoquinone, CO, MeOH, RT, 69 %; b) CSA, MeOH, 80 8C, then evaporation, benzene, 80 8C, 100 %; c) AcCl, pyridine, CH 2 Cl 2 , RT, 95 %; d) P 2 O 5 , CH 2 Cl 2 , RT, 71 %; e) ClCH 2 COCl, pyridine, CH 2 Cl 2 , RT, 99 %; f) P 2 O 5 , CH 2 Cl 2 , RT, 75 %; g) Et 3 N, MeOH/CH 2 Cl 2 (1:3 v/v), 40 8C; h) MgI 2 ·OEt 2 , benzene, 80 8C, 2 steps 56 %. CSA = camphorsulfonic acid, CA = chloroacetyl. Angewandte Chemie 2089

Recent Advances in Total Synthesis of Bioactive Furo[3,2‐b]furanone Natural Products

“…Total synthesis of (±)‐lactonamycin ( 14 ) and (+)‐lactonamycin Z ( 202 ) was recently accomplished by Nakata and co‐workersstarting from readily accessible salicylate derivative 233 (Scheme ) . The phenolic OH was converted to aldehyde 234 via formation of triflate, vinyl Stille coupling and ozonolysis.…”

“…Total synthesis of (�)-lactonamycin (14) and (+)-lactonamycin Z (202) was recently accomplished by Nakata and co-workersstarting from readily accessible salicylate derivative 233 (Scheme 30). [68] The phenolic OH was converted to aldehyde 234 via formation of triflate, vinyl Stille coupling and ozonolysis. Ester group hydrolysis led to lactol 235 which via sequential reductive amination with methyl amine, conversion to corresponding isopropylcarbamate and anhydride formation delivered the homophthalic anhydride 236.…”

The chemistry of isoindole natural products

“…Several total syntheses of 215 and 217 were reported in recent years [161] (and references therein). The group of Danishefsky was the first to report a diastereoselective synthesis of lactonamycinone ( 214 ) employing a Diels–Alder reaction [162–163].…”

“…The recently published total synthesis of lactonamycin ( 215 ) and lactonamycin Z ( 217 ) by Saikawa and Nakata is based on a late-stage glycosylation strategy (Scheme 29). This enables the specific variation of the sugar components and gives access to various lactonamycin derivatives [161]. …”

Synthesis and Application of [3.3.0]Furofuranone in Total Synthesis

“…As reported by Nakata (Scheme ), compound 89 underwent Pd‐catalyzed oxidative cyclization and methoxycarbonylation to form an exocyclic α,β‐unsaturated ester, which was finally subjected to lactonization mediated by camphorsulfonic acid (CSA) in MeOH at 80 °C to give the crucial intermediate 90 towards the synthesis of lactonamycin.…”