Synthetic Studies on the Sulfur-Cross-Linked Core of Antitumor Marine Alkaloid, Discorhabdins: Total Synthesis of Discorhabdin A

Abstract

Discorhabdins and prianosins have been isolated from marine sponges such as New Zealand sponges of the genus Latrunculia, Okinawan sponge Prianos melanos, and Fijian sponge Zyzzya cf. Marsailis. Among the various discorhabdins (A ± R) isolated, discorhabdins A (1), [1a,b,d] B, [1b] D, [1c] Q, [1e] and R [1f] have a unique sulfur-containing fused-ring system incorporating an azacarbocyclic spirocyclohexadienone and a pyrroloiminoquinone system (Scheme 1), and show potent antitumor activity. [2] The discorhabdins have

Advances in Synthetic Applications of Hypervalent Iodine Compounds

“…Hypervalent iodine-induced dearomatization of phenolic substrates in the intramolecular mode is a powerful synthetic tool for the construction of spirodienone fragment. Numerous oxidative spirocyclizations of phenolic substrates containing an internal oxygen, ,,− nitrogen, ,− or carbon nucleophile − have been reported and utilized in natural product syntheses. Representative examples include the preparation of spirolactone 221 from amino acid 220 , spirolactam 223 from phenolic 2-oxazolines 222 , and spirocyclic 225 from phenols 224 (Scheme ).…”

“…The intramolecular coupling reaction provides a powerful synthetic tool for the preparation of various carbocyclic and heterocyclic compounds. − Recent examples of the intramolecular oxidative coupling of phenolic ethers include the following: (1) oxidative coupling of tetramethoxy-substituted phenyl acetate 240 affording the corresponding tetramethoxydibenzooxepione 241 , (2) cyclization of N-protected indoles 242 to pyrroloiminoquinones 243 , and (3) cyclization of benzylsulfide 244 to dihydrobenzothiophene 245 (Scheme ). Coupling products 243 and 245 have been employed in the total synthesis of the potent cytotoxic makaluvamine F. ,− …”

Synthesis of the Marine Pyrroloiminoquinone Alkaloids, Discorhabdins

“…For the synthesis of prianosin B ( 2 ), the construction of the 16,17-dehydropyrroloiminoquinone structure is an important issue. We have succeeded in the first total synthesis of the sulfur-containing discorhabdin, discorhabdin A [ 40 – 43 ]. We postulated that the prianosins and discorhabdins with the 16,17-dehydropyrroloiminoquinone moiety can be synthesized by dehydrogenation of the pyrroloiminoquinone of the discorhabdin A ( 1 ) or discorhabdin A intermediate ( Scheme 22 ).…”

“…Because of their prominent potent antitumor activity and unusual ring structure, pyrroloiminoquinone alkaloid synthesis has attracted the interest of many organic chemists, and over the last decade, the total synthesis of a few of them as well as synthetic approaches has appeared. Our group accomplished the first total syntheses of discorhabdin C ( 7 ) [ 37 ], makaluvamine F [ 38 , 39 ] and discorhabdin A ( 1 ) [ 40 – 43 ]. In 2009, we also accomplished the first total synthesis of prianosin B ( 2 ) [ 44 ].…”

‘Reverse biomimetic’ synthesis of l-arogenate and its stabilized analogues from l-tyrosine

“…These examples produced spirolactones, 10 spirolactams 11 and a spirodienone carboxylic acid precursor to the natural product discorhabdin. 12…”