Studies toward the total synthesis of cyclodidemniserinol trisulfate. Part II: 3,5,7-Trisubstituted 6,8-dioxabicyclo [3.2.1] octane core structure construction via I2-mediated deprotection and ring closure tandem reaction

Synthesis of the C5–C30 fragment of cyclodidemniserinol trisulfate via I2-mediated deprotection and ring closure tandem reaction

“…7 The C 5 -C 30 fragment can be further disconnected into smaller subunits 5 (epoxide fragment) and 6 (thioacetal fragment), which can be joined by an S N 2 epoxide opening reaction followed by an I 2 -mediated deprotection and intramolecular ketal formation tandem reaction according to our established approaches in the early exploration work. 8 So, our approach disconnects the natural product into four parts: Fragment A (5), which contained an epoxide group and could be synthesized from D-tartaric acid; Fragment B (6), containing a thioacetal group and two undetermined chiral centers; Fragment C (3), bearing a phosphonate at one terminus and a carboxylic acid at the other; Fragment D (4), the serine derivative. Because the structurally simple fragments 3 and 4 were conveniently synthesized by using the literature reported methods, 9,10 we reported herein the synthesis of fragments 5 and 6 and the following construction of the key portion C 5 -C 30 .…”

“…Since the vinyl ether can be removed under acidic condition, we continued the following coupling reaction with the isomerized compound. Taking advantage of our previous synthetic study results, 8 the generated hydroxyl group in 26 was protected as isovaleric ester, because isovaleroate group served as a stable protective group to resist the epimerization, furthermore, the isovaleroate group was naturally occurring on the natural product of cyclodidemniseriol.…”

“…We used to make much effort on constructing the core structure of 3,5,7-trisubstituted 6,8-dioxabicyclo [3.2.1] octane, 8,19 and have tried proton acid in polar solvent (such as HCl in MeOH) or Lewis acid in non-proton solvent (such as BF 3 $Et 2 O in Et 2 O) to catalyze the intramolecular ketal formation reaction. Finally, by judiciously making use of the special reactivity of iodine reagent, which can remove both thioketal group and ketal group, 20 we successfully established an efficient methodology to synthesize the 3,5,7-trisubstituted-6,8-dioxabicyclo [3.2.1] octane, featured with an I 2 -mediated deprotection and ring closure tandem reaction, including thioketal deprotection, acetonide deprotection and intramolecular ketal formation in one pot.…”

“…Finally, by judiciously making use of the special reactivity of iodine reagent, which can remove both thioketal group and ketal group, 20 we successfully established an efficient methodology to synthesize the 3,5,7-trisubstituted-6,8-dioxabicyclo [3.2.1] octane, featured with an I 2 -mediated deprotection and ring closure tandem reaction, including thioketal deprotection, acetonide deprotection and intramolecular ketal formation in one pot. 8 However, the I 2 -mediated formation of the 3,5,7-trisubstituted- existing in the precursor 27, we modified the I 2 -based methodology by adding NaHCO 3 into the I 2 -acetonitrile system. Then we applied the modified I 2 -mediated deprotection and ring closure tandem reaction to the synthesis of 3,5,7-trisubstituted-6,8-dioxabicyclo [3.2.1] octane containing C 5 -C 30 subunit.…”

An Efficient Stereoselective Total Synthesis of Synargentolide A and Its Epimer

“…The synthesis of synargentolide A (1) was initiated by converting d-tartaric acid (6) into olefin 7 following a reported method [6] C-NMR and MS). The physical and spectral properties of these compounds were identical to those reported earlier [4].…”