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. 2024 Aug 9;26(31):6614-6618.
doi: 10.1021/acs.orglett.4c02239. Epub 2024 Jul 30.

From Acyclic Intramolecular-[4 + 2]- to Transannular Bis-[4 + 2]-Cycloaddition of the Macrodiolide for the Stereoselective Synthesis of the Octahydronaphthalene Core of Polyenic Macrolactam Sagamilactam

Oscar Iglesias-Menduiña  1 , Diego Novegil  1 , Claudio Martínez  1 , Rosana Alvarez  1 , Angel R de Lera  1
Affiliations

From Acyclic Intramolecular-[4 + 2]- to Transannular Bis-[4 + 2]-Cycloaddition of the Macrodiolide for the Stereoselective Synthesis of the Octahydronaphthalene Core of Polyenic Macrolactam Sagamilactam

Oscar Iglesias-Menduiña et al. Org Lett. .

Erratum in

Abstract

The strategy for the synthesis of the octahydronaphthalene core of natural macrolide sagamilactam has unintentionally evolved from the acyclic intramolecular (IMDA) to the transannular (TADA) Diels-Alder reaction. Lewis acid-promoted IMDA of a protected 2Z,8E,10E-4,6,12-trihydroxy-2,8,10-decatrienal model with a diol of 4,6-anti relative configuration, as proposed by DP4+-based computational studies, afforded the cis-octahydronaphthalene diastereomer through the Re-endo approach. The 26-membered macrodiolide generated, under thermal reaction conditions, the trans-octahydronaphthalene by a double TADA reaction along the desired Si-exo orientation.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
A. Proposed structure of sagamilactam (1) and the putative biogenetic precursor (2).B. 1H-CMAE and 13C-CMAE values for the NMR simulations [B3LYP/6-31+G**-PCM(MeOH)] of 3.
Scheme 1
Scheme 1. Retrosynthetic analysis of the (Protected) Dihydroxyoctahydronaphthalene Model System 4
Scheme 2
Scheme 2. Synthesis of (2Z,4S,6R,8E,10E)-4,6,12-Trihydroxydodeca-2,8,10-trienal 5 and IMDA
Scheme 3
Scheme 3. Synthesis of Macrodiolide 31
Scheme 4
Scheme 4. Double TADA Cycloaddition of 26-Membered Macrodiolide 31Z to Octahydronaphthalene-Fused 10-Membered Macrodiolide 33 and Synthesis of Octahydronaphthalene 35
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