Cephalosporolide B Serving as a Versatile Synthetic Precursor: Asymmetric Biomimetic Total Syntheses of Cephalosporolides C, E, F, G, and (4-OMe-)G

Abstract

Cephalosporolide B (Ces-B) was efficiently synthesized and exploited for the first time as a versatile biomimetic synthetic precursor for the chemical syntheses of not only cephalosporolides C, G, and (4-OMe-) G via a challenging diastereoselective oxa-Michael addition but also the structurally unprecedented cephalosporolides E and F via a novel biomimetic ring-contraction rearrangement. These findings provide the first direct chemical evidence that Ces-B may be the true biosynthetic precursor of cephalosporolides.

Total Synthesis of Marine Natural Products: Cephalosporolides

“…All syntheses involved Yamaguchi marolactonization as a key step to construct the 8-membered lactone. The synthesis reported by Tong et al [34] is based on an oxidative ring expansion of b-hydroxyethers [35] as a key step to construct the 10-membered lactone. The rhododendrol 55 was protected as TBS ether 56 and then subjected to phenol dearomatization, desilylation, and subsequent oxa-Michael cyclization to provide bicyclic ether 57 as a single diastereomer (Scheme 10).…”

“…A similar chemistry was employed by Tong as described earlier (Scheme 10). [34] Finally, deprotection of the TBS group followed by regioselective reductive opening of the epoxide afforded cephalosporolide G 6 with the (3S,4R,9R) absolute configuration at the stereogenic centers.…”

“…d) Tong's synthesis of the originally proposed structure of cephalosporolide J (2014) Tong et al [45] used the earlier strategy [34] (Scheme 10) toward cephalosporolide J 9 that commenced from rhododendrol 55, which was converted through a known sequence into bicyclic ether 67' (Scheme 14). TMS protection of 67' followed by subsequent epoxidation with m-CPBA gave the bicyclic epoxy alcohol 73 as a single diastereomer.…”

Total Synthesis of Ascospiroketal A Through a AgI‐Promoted Cyclization Cascade

“…[1] The relative stereochemistry within the tricyclic core of the ascospiroketals was established from analysis of NOESY experiments and confirmed that these compounds are anomeric spiroacetals. Structurally, these compounds represent the most complex members of a small family of tricyclic 5,5-spiroacetals [2] that includes the cephalosporolides, [3] penisporolides, [4] and opaliferin, [5] for which several potentially useful biological activities have been ascribed. Thus, the relative stereochemistry of the three remote stereocenters remained undefined.…”

A Novel PCC-Catalyzed Process Involving the Oxidative Cleavage of an α-Bromomethyl-tetrahydrofuran Bond. Synthesis of (2S,3R)-2-{(R)-Bromo[(2R,3R,5S,6R)-3,5-dibromo-6-ethyltetrahydro-2H-pyran-2-yl]methyl}-5-oxotetrahydrofuran-3-yl Benzoate

“…Pyridinium chlorochroamte (PCC) is a well known oxidizing reagent. Although it is mostly used in the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively, it has also been employed in a number of other processes [5], and recently, we [6][7][8][9] and others [10][11][12][13][14] have disclosed its ability to catalyze new synthetically useful reactions. We were now interested in testing some oxidative methods previously developed in our laboratories [8, [15][16][17] on a number of structurally diverse molecular frameworks in order to access a selection of variously functionalized substances for structure-activity relationship studies [18].…”