85279-97-6Relevant academic research and scientific papers
Total synthesis of myxovirescin A1
Fuerstner, Alois,Bonnekessel, Melanie,Blank, Jarred T.,Radkowski, Karin,Seidel, Guenter,Lacombe, Fabrice,Gabor, Barbara,Mynott, Richard
, p. 8762 - 8783 (2008/04/03)
A convergent total synthesis of the antibiotic macrolide myxovirescin A1 (1) is described that is largely based on reagent- and catalyst-controlled transformations. This includes a highly regioselective Negishi reaction of dibromo-alkene 48 with an alkynyl-zinc reagent, and a palladium catalyzed alkyl-Suzuki coupling of the resulting enyne derivative 12 with the 9-BBN-adduct derived from alkene 61. The latter was obtained via an asymmetric hydrogenation of the chlorinated β-ketoester 49 and an anti-selective oxyallylation of the functionalized aldehyde 53 as the key steps. The preparation of the bis-borylated allyl-donor 57 used in the oxyallylation step, however, required careful optimization and led to important insights into the nature of the classical hydroborating agent "di(isopinocampheyl)borane (IpC2BH)". It was unambiguously shown by X-ray crystallography that in the solid state this compound is dimeric, but it is prone to undergo an essentially quantitative mono-deborylation when dissolved in CH 2Cl2 or benzene; its composition in ethereal solvents is even more complex as evident from 11B NMR data. Product 71 derived from 12 and 61 was elaborated into the enyne-yne derivative 75, which served as the substrate for an exquisitely selective ring closing alkyne metathesis reaction (RCAM) catalyzed by the molybdenum tris-amido complex 20 activated in situ with CH2Cl2. The resulting cyclic enyne 76 was subjected to a ruthenium catalyzed trans-hydrosilylation/proto-desilylation tandem. Although [Cp*Ru(MeCN)3]PF6 had previously been recommended as catalyst of choice for trans-hydrosilylation reactions of internal alkynes, this complex failed to afford the desired product, whereas its sterically less hindered congener [CpRu(MeCN)3]PF6 permitted the reaction to be performed in appreciable yield, but at the expense of a lower stereoselectivity. AgF-mediated proto-desilylation of the isomeric silanes 79 and 80 followed by cleavage of the remaining acetal protecting groups afforded myxovirescin A1 and its hitherto unknown 14Z-isomer 81, respectively.
Total Synthesis of Myxovirescins, 3. Coupling of the Two Key Fragment and Last Steps to Myxovirescins A1 and M2
Maestro, Miguel A.,Sefkow, Michael,Seebach, Dieter
, p. 731 - 738 (2007/10/02)
The last steps of a chiral building-block approach to the synthesis of myxovirescins A1, A2 and M2 are described.The "northwestern" parts, hydroxy sulfones (see preceding paper), and the "southeastern" parts, hydroxy aldehyde derivatives (first paper in this series), of the target molecules (Scheme 1) are first coupled by a Julia olefination (60 - 70percent yield); the resulting linear intermediates are oxidized (CH2OH --> CO2H) and deprotected for the final Yamaguchi macrolactonization (85 - 90percent yield, Scheme 2).Deprotection by hydrolysis of three different acetal moieties and chromatographic purification gave 20-mg amounts of synthetic myxovirescins M2 and A1 (Scheme 3) which were identical in all respects with authentic samples isolated and supplied to us by the team at the Gesellschaft fuer Biotechnologische Forschung in Braunschweig. - The total syntheses of the macrocyclic antibiotics consist of 62 and 66 steps, and the longest linear sequence of 25 steps was carried out in an overall yield of 2.5 and 0.85percent (over 85 and 80percent each step), respectively. - Key Words: Myxovirescin / Myxococcus virescens / Macrolides / Julia olefination / Yamaguchi macrolactonization / Myxovirescins M2 and A1 / Lactones / Lactams / Antibiotics
Total synthesis of myxovirescin A1
Williams, David R.,Li, Jie
, p. 5113 - 5116 (2007/10/02)
Stereocontrolled synthesis of myxovirescin A1 (1a), a 28-membered macrolactam lactone, is accomplished via a highly convergent route. Ring closure of the macrocycle is realized by macrolactamization using the Mukaiyama procedure.
Semisynthetic Myxovirescins: Exchange of the &α-Hydroxycarboxylic Acid Segment and Modification of the Ring Size
Borgschulte, Katrin,Trowitzsch-Kienast, Wolfram,Hoefle, Gerhard
, p. 69 - 81 (2007/10/02)
Partial degradation reactions of the macrocyclic lactam-lacton antibiotic myxovirescin A1 (1) yield the key building blocks 2 and 26.From these myxovirescin analoga are reconstituted with various alkyl groups at position C-2 with R and S configuration.Furthermore a ring-contracted (24) and a ring-enlarged (29) macrocycle are synthesized.The growth of E. coli is best inhibited by the natural myxovirescin A1 with a (2S) propyl substitution whilst 24 and 29 do not inhibit the growth of E. coli at all.
