Toward the synthesis of norzoanthamine: complete fragment assembly.
The complex marine alkaloid norzoanthamine (2) was envisioned to be assembled from three key building blocks: the C1-C5 fragment A, the C6-C10 fragment B, and the C11-C24 fragment C. The synthesis of fragment A was achieved in 14 steps and 33% overall yield from (R)-gamma-hydroxymethyl-gamma-butyrolactone. Fragment B was made in two steps from PMB-protected 4-pentynol in 76% yield. The C11-C24 fragment C was made from (S)-carvone via (R)-isocarvone in 18 steps (6% overall yield). The convergent stereoselective synthesis of the entire carbon framework (C1-C24) of the target molecule was achieved via the following assemblage. Alkenyl iodide 20 derived from the C11-C24 fragment C was coupled to fragment B (C6-C10) through a high-yielding Stille coupling reaction of these two sterically very demanding coupling partners, affording the key Diels-Alder precursor 24. The intramolecular Diels-Alder reaction proceeded smoothly in excellent yield and diastereoselectivity, generating the tricyclic trans-anti-trans perhydrophenanthrene motif of norzoanthamine (C6-C24). The final fragment coupling between lithiated fragment A (C1-C5) and aldehyde 40 (C6-C24) has also been successfully accomplished affording the entire carbon framework of the natural product.
Juhl
Martin
M
Department of Chemistry, Technical University of Denmark, Building 201, Kemitorvet, DK-2800 Kgs.Lyngby, Denmark.
Monrad
Rune
R
Søtofte
Inger
I
Tanner
David
D
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D001381:Azepines; D006576:Heterocyclic Compounds, 4 or More Rings; D011804:Quinolines; C400280:norzoanthamine