Crystal and Molecular Structures of Two Isomorphous Solvates of the Macrolide Antibiotic Borrelidin: Absolute Configuration Determination by Incorporation of a Chiral Solvent in the Crystal Lattice

Abstract

Crystal structures of two isomorphous solvates of the macrolide antibiotic borrelidin [ borrelidin 3-methylbutan-1-ol (A) and borrelidin (S)-2-methylbutan-1-ol (B)] have been determined from X-ray diffractometer data recorded at 294 and 152 K respectively. Crystals are monoclinic, space group P21, with a 13.501(2), b 12.000(2), c 11.863(2) � , β 110.76(1)� [(A); T = 294 K], and a 13.565(2), b 11.646(2), c 11 .376(3) �, β 109.76(1)� [(B); T = 152 K], (Z = 2). The structures were solved by direct-methods procedures and refined by full-matrix least-squares analysis to conventional R-factors of 0.061 [(A), 2676 reflections] and 0.048 [(B), 2851 reflections]. The absolute configuration of borrelidin follows from the known chirality of the (S)-2-methylbutan-1-ol solvent in (B), and is 3S,4S,6S,8R,1OS,11R,17S,18R,22R. The unusual structural and stereochemical features of borrelidin are discussed in relation to other macrolide antibiotics.

Total synthesis of the cytotoxic cyclodepsipeptide (-)-doliculide: The “ester” effect in acyclic 1,3-induction of deoxypropionates

“…Doliculide (14) and borrelidin (15)(16)(17) are the only known examples of macrocyclic natural products that contain two and three deoxypropionate units, respectively, within their carbon frameworks (Fig. 1).…”

Formal total synthesis of borrelidin: synthesis of C1–C11 fragment via desymmetrization strategy

“…3 It has reduced polypropionate moiety with four methyl groups possessing a distinctive syn/syn/anti relationship, a Z/E cyanodiene unit at C12-C15, and a cyclopentane carboxylic acid subunit at C17. Borrelidin possesses antiviral, 4 antibacterial activity, 1,5 in addition to anti-angiogenesis effects 6 and is found to display inhibitory activity toward cyclin-dependent kinase Cdc28/Cln2 of Saccharomyces cerevisiae.…”

Chemoenzymatic Synthesis of the C3–C11‐Fragment of Borrelidin

“…The structure was determined in 1967 by Keller-Schierlein, [11] and Anderson and co-workers solved the absolute configuration by X-ray crystal structure analysis. [12] Additionally to fermentation, [9] a variety of synthetic approaches to 1 have been developed [13][14][15][16][17][18] with the first total synthesis reported in 2003 by Morken. [19] Particularly, the stereoselective formation of the polyketide subunit, that is, the C3-C11 fragment in 1, has been intensively investigated.…”