Synthesis and Conformational Analysis of Geodiamolide Analogues

Marimganti, Srinivasa; Wieneke, Ralph; Geyer, Armin; Maier, Martin E.

doi:10.1002/ejoc.200700024

Cited by 16 publications

(12 citation statements)

References 34 publications

(24 reference statements)

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“…After concentration of the reaction mixture, macrolactam formation on the residue was carried out in DMF (0.001 M) in presence of TBTU, HOBt and Hünig’s base. [31, 32] After work-up the crude cyclic depsipeptide was treated with TBAF in THF to cleave the phenolic triisopropylsilyl ether. Careful inspection of the NMR data showed that macrocycle 2a did not correspond to natural chondramide A.…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis and Configurational Assignment of Chondramide A

Schmauder

Sibley

Maier

2010

Chemistry A European J

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The first total synthesis of the cyclodepsipeptide chondramide A (2 b) is described. This depsipeptide is composed of four subunits, namely L‐alanine, N‐Me‐D‐tryptophan, 3‐amino‐2‐methoxy‐propionic acid (β‐tyrosine derivative), and a 7‐hydroxy‐alkenoic acid. While the configuration of the stereogenic centers in the 7‐hydroxy‐alkenoic acid were known, the configuration of the tyrosine derivative required clarification and turned out to be (2S,3R) or (2L,3L), respectively. The synthesis of the 3‐amino‐2‐methoxy‐3‐arylpropanoic ester 20 b relied on an asymmetric dihydroxylation yielding diol ent‐15 a followed by a regioselective Mitsunobu substitution leading to 3‐azido‐2‐hydroxypropanoate 18 b. We could also show that the ester bond in the seco compound 26 b can be fashioned by a Mitsunobu esterification by using hydroxy ester (7S)‐7 and the tripeptide acid 25 b. This synthesis should allow for the preparation of various analogues.

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Section: Resultsmentioning

confidence: 99%

Total Synthesis and Configurational Assignment of Chondramide A

Schmauder

Sibley

Maier

2010

Chemistry A European J

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“…Subsequently, 16 was reduced to alcohol 17 , protected as acetonide 18 , and desilylated and substituted to iodide 7 in 88 % overall yield. To prepare the ketone 8 as the addition counterpart of 7 , the known diol 19 was chemoselectively silylated, oxidatively cleaved, and mesylated to 8 in 79 % yield. Their coupling was achieved by transmetalation of 7 followed by sequential addition of LaCl 3 and 8 to provide a near 1:1 mixture of the adduct (hydroxy mesylate) 21 and the cyclized epoxide 22 .…”

Section: Figurementioning

confidence: 99%

The Total Synthesis of Inostamycin A

Jung

Lee

et al. 2016

Angew Chem Int Ed

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“…To prepare the ketone 8 as the addition counterpart of 7,t he known diol 19 [14] was chemoselectively silylated, oxidatively cleaved, and mesylated to 8 in 79 %yield. Subsequently, 16 was reduced to alcohol 17, protected as acetonide 18,a nd desilylated and substituted to iodide 7 in 88 %overall yield.…”

Section: Inostamycin Awas Isolated From the Fermentation Broth Ofmentioning

confidence: 99%

“…Subsequently, 16 was reduced to alcohol 17, protected as acetonide 18,a nd desilylated and substituted to iodide 7 in 88 %overall yield. To prepare the ketone 8 as the addition counterpart of 7,t he known diol 19 [14] was chemoselectively silylated, oxidatively cleaved, and mesylated to 8 in 79 %yield. Their coupling was achieved by transmetalation of 7 followed by sequential addition of LaCl 3 [15] and 8 to provide anear 1:1mixture of the adduct (hydroxy mesylate) 21 and the cyclizede poxide 22.T he generated mixture was treated with base in situ to furnish the epoxide 22 in 88 % yield without detection of its diastereomeric product.…”

mentioning

confidence: 99%

The Total Synthesis of Inostamycin A

Jung

Lee

et al. 2016

Angewandte Chemie

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The first total synthesis of inostamycin Ai s described. With efficient and stereoselective synthetic routes to aldehyde 3 and ketone 4 developed through asymmetric aldol reactions,a ddition reactions and reduction, and with chiral building blocks,t he two large fragments were coupled with remarkable anti stereoselectivity and efficiency by aldol condensation. The coupling reaction provided the complete carbon skeleton with all the requisite functional groups and stereogenic centers for inostamycin A. The two quaternary carbons at C20 and C16 of ketone 4 were elaborated in ahighly stereocontrolled manner by addition reactions of the transmetallated 5 to ethyl ketone 6 and the transmetallated 7 to methyl ketone 8,r espectively,i nw hicht he use of LaCl 3 for transmetallation was critical for high coupling efficiency.Inostamycin Awas isolated from the fermentation broth of Streptomyces sp.M H816-AF15 in 1990.[1] Its structure was first assigned by NMR spectroscopy and later confirmed by X-ray analysis of its sodium salt to manifest the relative stereochemistry.T he crystal structure of the sodium salt showed an ionophoric pseudo cyclic molecular shape,i n which the sodium cation coordinates to the two carboxylate oxygens,t he two hydroxyl oxygens at C9 and C17, the carbonyl oxygen, and the inner tetrahydrofuranyl oxygen.[1]Scrutiny of the reported crystal structure allowed us to identify am istakenly translated stereochemistry of the ethyl group at the C2 position. Accordingly,t he relative stereochemistry of inostamycin As hould be revised from 1 to 2 (Figure 1). Ther elated compounds,i nostamycins Ba nd C, were separated from the same microorganism af ew years later, and the structures were differentiated by aC 2m ethyl substituent and am issing carboxylic acid group,r espectively.[2] It is likely that the C2 stereochemistry of inostamycin Bs hould also be corrected. Inostamycins are known to display antimicrobial and cytocidal activities,w ith inostamycin As howing the highest potency.[2] Only inostamycin A exhibits inhibitory activity against cytidine-5'-d iphosphate 1,2-diacyl-sn-glycerol (CDP-DG):inositol transferase to reduce phosphatidylinositol turnover, and restrain cell proliferation and transformation.[3a] Other prospective physiological properties of inostamycin Ai nclude restoration of paclitaxel cytotoxicity to augment apoptosis, [5] and cytostatic suppression of tumor recurrence.[3b] Thes tructural complexity,anticancer agents from multidrug resistance, [4] and potentiation of and pharmacological potential of inostamycin A attracted us to attempt its synthesis.H erein, we describe the first total synthesis of inostamycin A 2.[6]Our retrosynthetic blueprint was framed by severing the C9 À C10 bond of 2 to engender the aldehyde part 3 and the ethyl ketone part 4 (Scheme 1). Forsynthesis of 3,weplanned to cleave the C2 À C3 and C5 À C6 bonds,w hich would be restored with the four stereogenic centers by aldol condensations.T he remaining asymmetric centers were to be supplied by two enantiome...

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Synthesis and Conformational Analysis of Geodiamolide Analogues

Cited by 16 publications

References 34 publications

Total Synthesis and Configurational Assignment of Chondramide A

Total Synthesis and Configurational Assignment of Chondramide A

The Total Synthesis of Inostamycin A

The Total Synthesis of Inostamycin A

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