Synthesis of (+)-myrtopsine, (+)-7,8-dimethoxymyrtopsine and related benzofuran natural products, (+/-)-thallusin and (-)-chaetominine. A formal, biomimetic synthesis of polygalolides A and B. Structure revision and total synthesis of (-)-berkelic acid

The first syntheses of (+)-myrtopsine and (+)-7,8-dimethoxymyrtopsine have been achieved by halogen-metal exchange of 3-iodo-4-methoxy-quinolin-2(1 H)-ones with i-PrMgCl followed by addition of ( R)-3,3-dimethyloxirane-2-carboxaldehyde. This sequence controls the absolute stereochemistry at C-2 but gives a mixture of cis and trans-dihydrofurans.;Cyclization of farnesylacetone with 5 equiv of FSO3H in 2-nitropropane afforded (+/-)-sclareol oxide, which was elaborated to biologically active (+/-)-thallusin using the procedures developed by Dr. Xiaolei Gao in our lab to convert (+)-sclareol oxide to biologically inactive ent -thallusin.;Reaction of a pyranulose and Et3N gave an oxypyrylium zwitterion, which underwent a stereo- and regiospecific [5 + 2] cycloaddition with alpha-methylenebutyrolactone. Treatment of the product with Cs2CO3 hydrolyzed the lactone and acetate and the hydroxyethyl group added conjugatively to the enone. Lactonization on acidification afforded a late intermediate reported by Hashimoto, thereby completing a formal, biomimetic synthesis of polygalolides A and B.;Chaetominine is closely related to the tetrapeptide alkaloids fumiquinazolines A and B. The first synthesis of (-)-chaetominine was achieved in seven steps from a tricyclic hydroxy imidazolidinone fumiquinazoline intermediate. The key step of chaetominine synthesis is the cyclization of an amino ester with catalytic DMAP in toluene at reflux to give a delta-lactam.;A fully functionalized gamma-butyrolactone was prepared by Hanessian's procedure and converted to a ketal aldehyde. An oxa-Pictet-Spengler cyclization of the ketal aldehyde and a 2,6-dihydroxy benzoic acid gave a single diastereomer, which was converted to an aldehyde by a three-step sequence. Reaction of the aldehyde and a trimethylsilyl ketene acetal by Kiyooka's procedure afforded only two of the four possible aldol adducts, from which a pure beta-hydroxy ester and the diastereomer at C-22 were each isolated in 40% yield. Oxidation and deprotection of these two epimers provided (-)-berkelic acid and 22- epi-berkelic acid, respectively. The synthesis proceeds in only 13 linear steps in 2% overall yield, reassigning the stereochemistry at C-18 and C-19, tentatively assigning the relative stereochemistry at C-22, and establishing the absolute stereochemistry.