Total Synthesis of (+)-Petromyroxol, (−)-iso-Petromyroxol, and Possible Diastereomers

Abstract

The total synthesis of (+)-petromyroxol ( 1 ) and its seven diastereomers including the (−)- iso -petromyroxol ( 2 ) is described. The employed strategy involves the use of easily available C5-epimeric epoxides 5 and 5′ and nonselective anomeric C1-allylation, proceeding with or without inversion at C2, thereby giving the possibility of synthesizing all possible diastereomers. Extensive two-dimensional (2D) NMR analyses of all eight diastereomers have been carried out to assign the chemical shifts of the central carbons and the corresponding attached hydrogens and to learn how the C/H-chemical shifts of the tetrahydrofuran ring were influenced by the adjacent centers.

Unified Approach for the Total Synthesis of Bis-THF C15 Acetogenins: A Chloroenyne from Laurencia majuscula, Laurendecumenyne B and Laurefurenynes A/B

“…Rf = 0.3 (40% EtOAc/petroleum ether); [α] 25 D: 43.7 (c = 0.9, CHCl3). 1 H NMR (400 MHz, CDCl3): = 5.84 (ddt, J = 16.8, 9.9, 6.9 Hz, 1H), 5.25 (ddd, J = 5.…”

“…The 2,2'-bis-tetrahydrofuranyl C15 acetogenins constitutes as special acetogenin class of natural products that are isolated from different marine sponges. [1][2][3][4][5] Due to the presence of multiple stereogenic centres and conformational flexibility around/of THF rings, these bis-THF acetogenins pose challenges for their structural elucidation as well as synthesis. 1 The unambiguous structure elucidation of these bis-THF acetogenins by NMR analysis alone is quite a challenge and structural revision is a common aspect in case of several of these natural products.…”

“…It also highlights the need for simple approaches for assembling the bis-THF with a provision to manipulate the functional groups/stereochemistry. 11 In this context, as a part of our ongoing program on the total synthesis of mono-/bis-THF natural products employing easily accessible carbohydrate building blocks and devising the flexible strategies that allow the synthesis of possible diastereomers for generating 13 C NMR database, [12][13][14][15] the total synthesis of these natural products 1-5 has been planned with the prerequisite of designing a unified approach from a common intermediate. As shown in Figure 1, the all five natural products contain the same stereochemistry (except notoryne) at the four oxygen-attached carbons of the THF rings and the stereochemistry/functional groups at the other two stereogenic centers vary.…”

“…[1][2][3][4][5] Due to the presence of multiple stereogenic centres and conformational flexibility around/of THF rings, these bis-THF acetogenins pose challenges for their structural elucidation as well as synthesis. 1 The unambiguous structure elucidation of these bis-THF acetogenins by NMR analysis alone is quite a challenge and structural revision is a common aspect in case of several of these natural products. [2][3][4][5][6][7][8][9][10] For example, a fused dihydropyran structure proposed for (Z)-elatenyne 2,6 (1, isolated in 1986), chloroenyne from L. Majuscula 3,7 (2, isolated in 1993) and laurendecumenyne B 2b, 6 (3, isolated in 2007) were reassigned to the bistetrahydrofuran core by Burton's group with the help of ab initio prediction of 13 C NMR chemical shifts coupled with the total synthesis.…”

“…Rf = 0.3 (80% EtOAc/petroleum ether). [α] 25 D: 17.0 (c = 0.2, MeOH) 1. H NMR (400 MHz, CDCl3): = 6.24 (dt, J = 15.9, 7.4, Hz, 1H), 5.59 (ddd, J = 15.9, 3.6, 1.5 Hz, 1H), 4.40 (ddd, J = 8.2, 6.2, 2.0 Hz, 1H), 4.16 (dt, J = 10.0, 2.4 Hz, 1H), 4.12 (dt, J = 6.5, 3.1 Hz, 1H), 4.064.00 (m, 1H), 3.90 (td, J = 6.5, 3.6 Hz, 1H), 3.54 (td, J = 6.9, 2.5 Hz, 1H), 2.83 (d, J = 1.9 Hz, 1H), 2.502.34 (m, 2H), 2.23 (ddd, J = 14.0, 10.0, 5.2 Hz, 1H), 2.12 (br.…”