Benzannulated spiroketal natural products: isolation, biological activity, biosynthesis, and total synthesis

Abstract

A review discussing the isolation, biological activity, biosynthesis, and total synthesis of naturally occurring benzannulated spiroketals.

Preparation of benzannulated spiroketals by gold(III) catalyzed spirocyclization of alkynyl diols

“…The present first known study on gold(III)-oxazoline catalysed tandem spiroketalization shows that Au(III)-BOX (11a-e) and Au(III)-PYR-OX (13) complexes are highly efficient catalyst for intramolecular dihydroalkoxylation of alkynyl diols (7,9) to give aromatic 5,6-spiroketal products (14 and 15/16). The mono-and dibenzannulated spiroketals (14 and 15/16) were obtained in high yields (> 90%) by rapid conversion of symmetrical and nonsymmetrical alkynyl diols, respectively (7,9). Minor enantioselectivity (up to 6% ee) was observed with the Au(III)-BOX-BF4 and Au(III)-PYR-OX catalysts (11a, 13).…”

“…Symmetrical alkyne substrate. With both substrates (7,9) and gold(III) catalysts 11a-e, 13 in hand, the reaction conditions for the dihydroalkoxylation reaction were screened. The symmetrical alkynyl diol 7 was treated with gold(III) complexes 11a-e and 13 (Scheme 3) in various solvents at room temperature to give the expected dibenzannulated 5,6-spiroketal 14 (spiro[isobenzofuran-1,3'-isochromane, Table 1).…”

“…6 The presence of the particular spiroketal fragment was correlated to increased inhibition of human telomerase by the rubromycin family of natural products. The specific chemistry of chiral benzannulated spiroketals has received much attention because they are common key substructures in bioactive natural products 7 such as rubromycin (4), a 5,6-spiroketal comprised of an oxygenated naphthoquinone moiety linked with an isocoumarin fragment. The synthesis of spiroketals has received considerable attention.…”

A Silver‐Catalyzed Modular Intermolecular Access to 6,6‐Spiroketals

“…For example, Griseusin G and especially F have been found to have cytostatic properties with excellent efficiency against human cell lines of melanoma, breast carcinoma, pancreatic cancer, renal carcinoma and colon cancer. [5] Still, predicting structure-activity relation remains a challenge for biological active molecules. [4] Recently, Brimble et al published insightful reviews on the potential of Griseusin derivates [3] and spiroketals in natural products.…”

“…[4] Recently, Brimble et al published insightful reviews on the potential of Griseusin derivates [3] and spiroketals in natural products. [5] Still, predicting structure-activity relation remains a challenge for biological active molecules. This holds true for Griseusin derivates, too.…”