Asymmetric synthesis of Goniothalesdiol A from (R)-2,3-O-cyclohexylidine glyceraldehyde

Direct Access to 2,3,4,6-Tetrasubstituted Tetrahydro-2H-pyrans via Tandem SN2′–Prins Cyclization

“…Moreover, the introduction of four different substituents in the tetrahydro pyran ring may indeed affect its three-dimensional molecular structure and, therefore, its biological activity. , Also, it provides excellent opportunities toward the introduction of molecular complexity. However, despite their attractiveness as synthetic targets, there have been few reports on the synthesis of 2,3,4,6-THPs using Prins cyclization conditions, − most notably due to the existence of competitive pathways that result in racemization problems and/or mixtures of undesired products. ,− Additionally, the creation of new stereogenic centers, controlled by pre-existing stereochemical features, is often a challenge in acyclic molecules since it is not always easy to reduce the number of degrees of rotational freedom in a molecule . In the present work, we report our findings on the stereocontrolled one-pot synthesis of 2,3,4,6-THPs.…”

Protecting-Group-Free Total Synthesis of Goniothalesdiol A

“…After a highly stereoselective dihydroxylation reaction, 16b,c goniothalesdiol A 1 was obtained in 92% yield (Scheme 2), whose spectral data were in good agreement with those reported in the literature. 7,8,17 In summary, a concise asymmetric total synthesis of goniothalesdiol A 1 was achieved in six steps and 30% overall yield. The cis-2,6-disubstituted pyran moiety was effectively constructed via silyl-Prins reaction, while C-3 and C-4 vicinal dihydroxy groups were secured by stereo- selective dihydroxylation.…”

“…7 Fadnavis synthesized goniothalesdiol A in 22% overall yield and ten steps via stereoselective allylation, Grignard reaction, cross-metathesis and intramolecular oxy-Michael addition as key steps. 8 As part of our ongoing program towards the syntheses of bioactive pyran-and pyranonetype natural products, 9,10 herein we report a concise and protecting-group-free asymmetric total synthesis of goniothalesdiol A 1, in which silyl-Prins cyclization 11 was used as the key step.…”

“…6 There were two independent synthetic efforts toward goniothalesdiol A reported by Yadav and Fadnavis. 7,8 In the Yadav's synthesis, goniothalesdiol A was achieved in 11 steps and 35.1% overall yield by using Chan alkyne reduction, Sharpless kinetic resolution and intramolecular oxy-Michael addition as key steps. 7 Fadnavis synthesized goniothalesdiol A in 22% overall yield and ten steps via stereoselective allylation, Grignard reaction, cross-metathesis and intramolecular oxy-Michael addition as key steps.…”