Biomimetic-Type Synthesis of the Racemic Non-Aromatic Angucyclinones of the SF 2315 and SS 228Y Types

Abstract

The biomimetic‐type aldol reaction of the tricyclic (E)‐configured precursors 6a/b gave the racemic nonaromatic angucycline derivatives 11‐13 of the SF 2315 and SS 288Y types. Chelate controlled conditions in the cyclization of 6b led to the regioisomeric product 10.

A Tribute to Prof. Karsten Krohn

“…Synthesis of natural products, quinone-antibiotics (anthracyclines 3, angucyclines 4, anthrapyranones 5, structure-activity relationships, biotransformations of precursors 6, biomimetic synthesis) and of other pharmacologically interesting compounds (NAD analogues). [3][4][5][6] 2. Chemistry of sugars (C-Glycosides, O-Glycosides); use of carbohydrates in natural product chemistry (7) 7 , conversion of sugars to carbocycles (8, 9) 8 and other starting materials for the synthesis of macrolides and other biologically important molecules (renewable raw materials).…”

Biomimetic Synthesis of Deca- and Dodecaketide-Derived Quinone Antibiotics

“…The desired nonaromatic angucylines were finally isolated when the reaction temperature was lowered to Ϫ45 to Ϫ60°C. [97] The reaction behavior of the (Z) isomer 77, with two trans-configured ketide chains attached to C-1 and C-2, was studied first. Virtually no reaction occurred below Ϫ35°C, while very slow conversion was observed above Ϫ25°C in 0.2  methanolic KOH.…”

“…Scheme 16. Aldol reactions of the transand cis-diketones 77 and 78 under chelation-controlled and chelate-breaking conditions [97] In the next series, the influence of catalytic amounts of bases on the (E) isomer 78, with cis-alkyl chains at C-1 and C-2, was studied. In the first experiment, chelate-controlled conditions (LiH in THF) were employed.…”

“…The synthesis of the natural pigment was completed by cleavage of the protecting groups by means of a short melt in AlCl 3 /NaCl at 150°C to yield the natural product G-2A (97).…”

Untitled

“…[8] In WP 3688-2 (2), the hydroxy groups at C-3 and C-4 a are assumed to be in a trans configuration, as opposed to the more common cis arrangement in aquayamycin (1) and related congeners. [14] However, with the exception of model studies in which only parts of the systems were constructed, [15,16] no synthesis has been reported of the entire benz[a]anthracene system, including the two hydroxy groups at C-4 a and C-12 b. [10] The assembly of the SF 2315B ring system, which lacks the hydroxy group at C-12 b in 2, was achieved by Sulikowski et al [11] and by our group, [12,13] using strategies based on Diels ± Alder reactions.…”