Eine generelle Sulton‐Route zu den Pamamycin‐Makrodioliden – Totalsynthese von Pamamycin‐621A und Pamamycin‐635B

Total Synthesis of Pamamycin‐649B

“…Retrosynthetic disconnection of 1 f led to the silylated larger hydroxy acid 2 that also occurs in pamamycin‐635F ( 1 d ) and ‐649A ( 1 e ) as well as to the benzyl ester 3 or its C2′ epimer 4 (Scheme ). Since the more readily available C2′ epimeric smaller fragment 4 had previously been used successfully in a streamlined total synthesis of pamamycin‐621A ( 1 b ),6a we felt that it could also be applied to a corresponding shortened access to pamamycin‐649B ( 1 f ).…”

“…Sultone 5 that already served as a building block for the pamamycins 1 a – c ,3a, 5c, 6a was treated with two equivalents of ethyllithium, which induced a domino elimination/alkoxide‐directed 1,6‐addition to yield the bicyclic compound 6 (Scheme ). Ozonolysis of this cyclohexene followed by eliminative workup at reflux in dichloromethane afforded a single hemiacetal 7 .…”

A Convergent Strategy for the Pamamycin Macrodiolides: Total Synthesis of Pamamycin‐607, Pamamycin‐593, and Pamamycin‐621D Precursors

“…Similarly, a late-stage modification in the synthesis of 2 and 5 [7] should be a viable route for the introduction of alternative substituents at C9 and C2'. These modifications are complementary to those recently reported by Metz and co-workers, [6] and thus our efforts complete the available tools required for the preparation of the structurally and biologically intriguing pamamycin macrodiolides. The total synthesis of pamamycin-621D (1 b) and -593 (1 c) starting from precursors 4 b and 4 c, respectively, are in progress in our group.…”

“…Metz and coworkers described the synthesis of pamamycin-621A and pamamycin-635B by means of their sultone-based strategy. [6] Herein we describe the asymmetric total synthesis of pamamycin-607 (1 a) from enantiomerically pure (S)-p-tolyl methyl sulfoxide as the only chiral starting material and illustrate the potential of our strategy for an analogous synthesis of pamamycin-621D (1 b) and pamamycin-593 (1 c) by the preparation of advanced precursors.…”

A Convergent Strategy for the Pamamycin Macrodiolides: Total Synthesis of Pamamycin‐607, Pamamycin‐593, and Pamamycin‐621D Precursors

“…On the other hand, the promising biological properties of the pamamycins call for the development of general routes to these molecules to establish structure–activity relationships, improve the pharmacological properties, and probe their mode of action. Metz and co‐workers described the synthesis of pamamycin‐621A and pamamycin‐635B by means of their sultone‐based strategy 6. Herein we describe the asymmetric total synthesis of pamamycin‐607 ( 1 a ) from enantiomerically pure ( S )‐ p‐ tolyl methyl sulfoxide as the only chiral starting material and illustrate the potential of our strategy for an analogous synthesis of pamamycin‐621D ( 1 b ) and pamamycin‐593 ( 1 c ) by the preparation of advanced precursors.…”