[Show abstract][Hide abstract] ABSTRACT: New synthetic strategies have been explored for the synthesis of the structural core of liposidomycins and caprazamycins, an intriguing class of complex nucleoside-type antibiotics. This structural core is comprised of a cyclic diazepanone system linked to an uridyl fragment. The various synthetic approaches have in common that they originate from an epoxy amide derived from uridine, obtained via reaction of uridyl aldehyde 19 with an amide-stabilized sulfur ylide. Two different strategies were shown to be efficient in constructing the diazepanone ring system: (a) a reductive amination of an epoxy aldehyde with N-methylamine with subsequent intramolecular oxirane ring opening and (b) a carbene insertion reaction of an acyclic diazoamine precursor.
The Journal of Organic Chemistry 02/2012; 77(3):1328-39. DOI:10.1021/jo202061t · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A new synthetic methodology of asymmetric epoxidation developed in our laboratories has been employed for the stereoselective synthesis of bengamide E (16) and analogues at the terminal olefinic position. In the event, the chiral sulfonium salt 30 was transformed into its corresponding sulfur ylide and reacted with aldehydes 21 and 44 to efficiently provide epoxy amides 31 and 45, respectively. To access the bengamides from these epoxy amides, we combined a synthetic strategy previously reported by us, using an olefin cross metathesis reaction to introduce various alkyl substituents at the terminal olefinic position of amide 33, with reactions mediated by palladium (Negishi or Suzuki couplings) from amide 49. This latter route of introduction of alkyl groups proved to be more efficient than the metathesis approach and allowed access to the generation of a wide array of new bengamide analogues.
The Journal of Organic Chemistry 08/2010; 75(16):5526-32. DOI:10.1021/jo100696w · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The synthesis of the polypropionate chain of Streptovaricin U (1) is described utilizing a new approach for the stereoselective synthesis of the macrolide-type antibiotics via sulfur ylides.
[Show abstract][Hide abstract] ABSTRACT: A new synthetic approach to the 5-epimers of muraymycins, a family of complex nucleoside-type antibiotics, is reported based on the synthesis of epoxy amides obtained via the reaction of sulfur ylides with the uridyl aldehyde derivatives 16, 29 and 30, followed by a subsequent oxirane ring opening reaction with diamines. This new strategy offers an excellent opportunity for the preparation of muraymycin analogues of biological interest. In fact, biological studies have revealed these 5′-epimers to be as biologically potent as the natural antibiotics, aside of representing a convergent and flexible route towards the natural congeners.
[Show abstract][Hide abstract] ABSTRACT: The regioselective opening reaction of 2,3-epoxyamides with various nucleophiles offers a variety of β-hydroxyamides with diverse synthetic utility depending on the introduced nucleophile. Due to the exclusive stereoselectivity in the formation of trans epoxyamides in reactions of aldehydes with stabilized sulfur ylides, we studied the isomerization of trans epoxyamides into the cis isomers with the objective of obtaining the corresponding syn opening products, which together with the anti isomers represent a variety of enantiomerically pure building blocks.
[Show abstract][Hide abstract] ABSTRACT: A synthetic approach to the tunicamycins, a complex family of nucleosides with potent antibiotic and antiviral activities is reported based on diazo chemistry. The corresponding precursors for the synthesis of tunicaminyl uracil derivatives, the non-stabilized diazo derived from 13 and the aldehyde derivative of uridine, compound 4, were prepared efficiently from commercially available D-galactal and uridine, respectively. After a high yielding coupling reaction to obtain the ketone 14, a stereoselective reduction provided the corresponding tunicaminyl uracil derivative 17a and its C-7 epimer 17b. The interconversion of the diazo and aldehyde functional groups in the requisite building blocks was similarly achieved to obtain the ketone 32, which after reduction yielded the corresponding 7-deoxy-6-hydroxy tunicaminyl uracil analogs 33a and 33b.
[Show abstract][Hide abstract] ABSTRACT: [reaction: see text] A synthetic approach toward the liposidomycins, a family of complex nucleoside-type antibiotics, is reported based on the synthesis of epoxy-amides derived from the reaction of sulfur ylides with the uridyl aldehyde derivative 6. To this end, the epoxy-amide derivative of indoline 14 was stereoselectively prepared and, after treatment with DDQ, transformed into the corresponding N-indole epoxyamide 15. The indole 15 provides ready access to a variety of structures related to the diazepanone core present in the liposidomycins by reaction with a variety of amines.