Synthesis cylindricine

A total synthesis for (+)-cylindricines A and B has been achieved. Alkylation of -trifluoromethanesulfonyl ester 409 afforded 410 (93MI273)... 

Three novel related marine alkaloids, halichlorine (1148) from the sponge Halichondria okadai (1177, 1178) and pinnaic acid (1149) and tauropinnaic acid (1150) from the bivalve Pinna muricata (1179), have been the objects of much synthetic interest in view of their pronounced biological activity (inhibition of the vascular cell adhesion molecule-1) (1180). Synthesis of these alkaloids led to both revision and confirmation of the original structures (1181,1182). The syntheses of the previously known chlorine-containing cylindricines have been reviewed (1183). 

Weinreb SM (2006) Studies on Total Synthesis of the Cylindricine/Fasicularin/Lepadifor-mine Family of Tricyclic Marine Alkaloids. Chem Rev 106 2531... 

Short Syntheses of (+)-Cylindricine and Formal Synthesis of (-)-Lepadiformine... 

The synthesis of a borylcopper(i) reagent from bis(pinacolato)diboron (B2pin2) and GuOAc was developed. The reagent used for the 1,4-addition to a,/3-unsaturated ketone 146230 led to an intermediate for the total synthesis of cylindricine C and 2-epicyclindricine G (Equation (52)).231... 

The analogous intramolecular 1,3-dipolar cycloaddition of the cyclic nitrone 155, in an attempt to get to intermediates useful for the synthesis of the cylindricine or lepadiformine natural products, unexpectedly gave by lb/3a bonding the bridged cycloadduct oxazocine 117 in 49% yield with total diastereocontrol. From this reaction, the fused cycloadduct through la/3b bonding (41%) was also isolated (Equation 8) <2000TA2625>. 

Trost, B.M. and Rudd, M.T. (2003) Chemoselectivity of the ruthenium-catalyzed hydrative diyne cyclization total synthesis of (+ )-cylindricine C, D, and E. Organic Letters, 5, 4599-4602. 

Reductive cyclization. Azide redu addition of the resulting amine to a a assemblage of fused-bridged tricycles hai synthesis of (—)-cylindricine. 

Scheme 2.102 PTC Phase-transfer catalyzed key step in the enantioselective synthesis of (+)-cylindricine C...

In 2006, Shibasaki and co-workers [91] developed phase-transfer-catalyzed asymmetric Michael addition of glycine Schiff base 237 and dienone 238 to afford dienone 240 in 84% isolated yield and 82% ee for the total synthesis of (+)-cylin-dricine C (242) and a formal synthesis of (—)-lepadiformine (244), using a chiral two center organocatalyst 239 (TaDiAS Tartrate-derived Di-Ammonium Salt) (Scheme 17.41). (+)-cylindricine C (242) was achieved three steps from 240 using... 

SCHEME 17.41. Phase-transfer catalyzed synthesis of (-t-)-cylindricine C (242) and (—)-lepadiformine (244). 

Shibasaki M, Shibuguchi T, Mihara H, Kuramochi A, Sakuraba S, Ohshrma T (2006) Short Synthesis of (-l-)-Cylindricine C by Using a Catalytic Asymmetric Michael Reaction with a Two-Center Organocatalyst. Angew Chem Int Ed 45 4635... 

Mihara H, Shibuguchi T, Kuramochi A, Ohshima T, Shibasaki M (2007) Short Synthesis of (-t)-Cylindricine C and Formal Total Synthesis of (-)-Lepadiformine. Heterocycles 72 421... 

A carbonylative coupling of a vinyl derivative was employed in a synthesis of cylindricine C 433 (Scheme 4.14). " In this case, the double Michael acceptor ability of the product was exploited to generate the tricyclic product, following protecting group manipulation and installation of nitrogen in the form of azide. Another synthesis of this molecule can be found in Scheme 11.89. 

Shibuguchi, M., Mihara, H., Kuramochi, A., Sakuraba, S., Ohshima, T., Shibasaki, M. (2006). Short synthesis of (-l-)-cylindricine C by using a catalytic asymmetric Michael reaction with a two-center organocatalyst. Angewandte Chemie International Edition, 45, 4635-4637. 

The mthenacyclopentatrienes, obtained by the oxidative cyclization of diynes, can also undergo an attack of other reagents than unsaturated molecules. In the presence of the complex [CpRu(CH3CN)3]PF6 and water, a hydrative diyne cyclization took place leading to a,p-unsaturated ketones [46-49] [Eq. (18)]. This reaction was applied to the total synthesis of (-i-)-Cylindricine C, D, and E [49]. 

As will be discussed, our pivotal intramolecular aza-[3+3] cycloaddition was remarkably efficient in providing the tricyclic scaffold of (—)-cylindricine C 384 and that of putative (—)-lepadiformine 389 (or (—)-4-deoxo-2-epi-cylindricine C) [170b,[198], yet this route could not be implemented in our synthesis of (—)-lepadiformine 385. To reconcile this, we devised a unified strategy to synthesize (—)-lepadiformine and (+)-cylindricines C-E (386-388) that... 

For the total synthesis of (—)-cylindricines, see Refs [204a,204h]. 

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