Total Synthesis of (−)‐Haouamine B Pentaacetate and Structural Revision of Haouamine B

Abstract

The enantiocontrolled total synthesis of (-)-haouamine B pentaacetate was accomplished via an optically active indane-fused β-lactam, which was prepared by a newly developed Friedel-Crafts reaction. Subsequent cleavage of the β-lactam and an intramolecular McMurry coupling reaction provided the core indane-fused tetrahydropyridine, which led to the elucidation of the structure, as proposed by Trauner and Zubía.

Marine natural products

“…Total synthesis has also led to revision of the structure of mandelalide A (Lissoclinum sp.) 851 to 1338 852 and conrmation of the revised structure of haouamine B (Aplidium haouarianum), [853][854][855] while the structures of distomadines A and B (Pseudodistoma aureum) 856,857 and synoxazolidinones A and B (Synoicum pulmonaria) 858,859 have been conrmed by synthesis. Synoxazolidinones A and C and S. pulmonaria co-metabolites pulmonarins A and B exhibited variable levels of anti-biofouling activity against a panel of test organisms, with synoxazolidinone C being particularly potent as both a growth and adhesion inhibitor.…”

Reactivity of 3‐Oxo‐β‐lactams with Respect to Primary Amines—An Experimental and Computational Approach

“…In 1972, Sheehan and Lo reported the preparation of benzyl 6‐oxopenicillanate as a source of new antibacterials, for example, by means of its further transformation to oxygen and carbon analogues of penicillin V . Interesting examples concerning the use of monocyclic 3‐oxo‐β‐lactams en route to biological applications comprise the total synthesis of the antifungal lipopeptide echinocandin B, serotonin reuptake inhibitor dapoxetine, and potent anticancer agent haouamine B . Furthermore, azetidine‐2,3‐diones are useful precursors for α‐hydroxy‐β‐amino acids, such as N ‐benzoyl‐(2 R ,3 S )‐phenylisoserine methyl ester, which is the renowned side chain of the antitumor agent Taxol .…”

Scalable Total Syntheses and Structure–Activity Relationships of Haouamines A, B, and Their Derivatives as Stable Formate Salts

“…However, (−)‐haouamine B ( 1 b ) was reported by Zubía et al. to be only slightly cytotoxic against the MS1 cell line (IC 50 =5 μg mL −1 ), although 1 b was unstable and characterized as its peracetate . Therefore, the mechanism underlying the weaker cytotoxicity and its intrinsic instability remains unknown but the presence of an additional hydroxyl group located on the C‐ring of the haouamine may be the source.…”

“…To omit the step to convert the aryl bromides 3 a and 3 b into corresponding boronic acids in situ, as reported previously, the 1‐cyclohexenylboron reagent 4 was prepared from enantiomerically pure Michael adduct 13 (Scheme ). According to Ley et al., monohydrolysis of 13 and subsequent decarboxylation afforded the monoester 14 .…”

“…for the intermolecular amination of primary alcohols, but has not been applied for the intramolecular variant . The use of excess CMPI and Hünig base under high dilution in acetonitrile (2 m m ) furnished Baran's and Tokuyama's intermediates 18 a and 18 b in excellent yields . Oxidative aromatization of cyclohexenone 18 a and 18 b followed by substitution of methyl with acetyl groups formed haouamine acetates 20 a and 20 b .…”