Saraine

Fig. 10 Various RCM substrates used in synthetic work directed to the marine alkaloid sarain (285)...

The ring system 413 is an intermediate in the synthesis of the tricyclic core of the marine alkaloids sarains A-C (Scheme 32) <1998JOC8096>. 

In their synthesis of (—)-sarain A, Overman et al. reported a similar difficulty in the oxidation of an alcohol proximal to a tertiary amine in the molecule Garg NK, Hiebert S, Overman LE (2006) Angew Chem Int Ed 45 2912... 

During the synthetic efforts of Heathcock and co-workers toward the complex marine alkaloid sarain-A (Scheme 3.80), he outlined an elegant intramolecular, azomethine ylide cycloaddition, as one of the key stages in the construction of the central core (76). Of the generation methods known for azomethine ylides, thermolysis of aziridines was selected in this instance. The azomethine ylide... 

Weinreb and co-workers (77) reported a similar protocol in the total synthesis of sarain A. The five-membered ring of the tricyclic central array was constructed via thermolysis of aziridine 244 to furnish the intramolecular [3 + 2]-cycloaddition product 245 in 73% as a single regio- and stereoisomer. Further chemical elaboration to 245 followed by FeCla induced cyclization delivered the advanced synthetic intermediate 247 (Scheme 3.83). 

A stabilized 4-oxazohne enolate can also undergo highly stereoselective Michael addition. Overman and co-workers studied this reaction in their synthesis of sarains A-C. Thus, deprotonation of the oxazoline 372 with LDA at 78 to 65 °C followed by reaction with the trans-ester 373 gave a single diastereomer of... 

The marine alkaloid sarain A 383 features an exceptionally challenging pentacyclic architecture (Figure 6). To date, 383 has not succumbed to a total synthesis. Two groups however have completed the tricyclic core of 383 and have annulated the western 13-membered ring using quite similar RCM approaches. " The results obtained with... 

The Mediterranean sponge Reniera sarai is a rich source of new macro-cyclic alkaloids, named sarains, which may be biogenetically related to petrosin (246) or araguspongins (236-243). The structures of sarains 1-3 (247-249) (2/0) and isosarain 1 (250) (211) were clarified on the basis of extensive spectroscopic analyses. The position of the double bond in 249 remains to be determined. The more polar fraction of this sponge contained three UV-absorbing alkaloids, named sarains A-C. The structure of the diacetylated derivative of sarain A (251) was established by X-ray analyis (2/2). 

From a Japanese sponge of the genus Haliclona two cytotoxic alkaloids, haliclamines A and B (252 and 253), were isolated (213). They are proposed to be biogenetic precursors of the petrosins or sarains. 

During studies aimed at the synthesis of the marine alkaloid Sarain A, Weinreb and co-workers391 reductively cleaved an N-benzyl amide in the presence of an /V-benzylamine using sodium in liquid ammonia [Scheme 8.185]. 

Sarains Haplosclerida sp. Anticancer, antibacterial, and insecticidal activities... 

Polycyclic amine alkaloids (3-alkylpiperidine alkaloids) containing a complex skeleton with several macrocyclic rings have been isolated from marine sponges. They include manzamines, sarains, haliclamine A and ingenamines. Their structures, synthesis and biochemical aspects have been recently reviewed [35]. Our focus, therefore, is on the biogenetic origin of the bis-pyridinium macrocycle and on the role of precursors in their biosynthesis, as summarized in the retrosynthetic analysis for manzamines demonstrated schematically in Fig.(23). 

Sarains A-C are a family of alkaloids isolated from marine sponges. J.K. Cha and co-workers accomplished the synthesis of the western macrocyclic ring of sarain To establish the C3 quaternary stereocenter, they treated the aldehyde substrate with formaldehyde in the presence of sodium carbonate. The aldehyde substrate underwent an aldol reaction followed by a Tishchenko reaction to provide the formate ester of the 1,3-diol product. This ester was hydrolyzed in situ under the reaction conditions and the 1,3-diol was isolated. 

An intramolecular allyl silane/N-sulfonyl iminium ion cyclization has also been used as a pivotal step in an approach to the tricyclic core of the unique marine alkaloid sarain A [46]. The starting material was aziridine ester 129 (Scheme 25) which was elaborated to amide 130. An important step in the synthetic strategy was thermolysis of 130 to an azomethine ylide, which underwent stereospecific intramolecular 1,3-dipolar cycloaddition with the Z-alkene to produce bicyclic lactam 131 [47]. This compound was then elaborated into allyl silane 132. It was then possible to replace the lactam N-benzyl functionality with a tosyl moiety, leading to 133, and subsequent reduction of the carbonyl group afforded the desired cyclization precursor a-hydroxy sulfonamide 134. Exposure of 134 to ferric chloride promoted cyclization to a single stereoisomeric tricyclic amino alkene 136 having the requisite sarain A nucleus. It is believed that the intermediate N-sulfonyl iminium ion cyclizes via the conformation shown in 135. 

Two groups of complex polycyclic 3-alkylpiperidine alkaloids have tricyclic or tetracyclic core structures resulting from the formation of two or three transannular bonds between the two piperidine rings of a bis-3-alkylpiperidine macrocycle. Saraine A (72), the... 

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