Novel synthesis of mevinolin-related compounds. Large-scale preparation of HMG-CoA reductase inhibitor L-679,336

DeCamp, Ann E.; Mills, Sander G.; Kawaguchi, Alan T.; Desmond, Richard; Reamer, Robert A.; DiMichele, Lisa; Volante, R. P.

doi:10.1021/jo00011a022

Cited by 30 publications

(13 citation statements)

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“…Reactions under standard Upjohn conditions (cat. OsO 4 , NMO), Sharpless asymmetric dihydroxylation conditions (commercial AD‐mix α or β, MeSO 2 NH 2 ), or methods involving basic additives (cat. OsO 4 , Me 3 NO, pyridine) did not result in any observable transformation of 3a .…”

Section: Resultsmentioning

confidence: 99%

Synthetic Adventures with 2‐C‐Branched Carbohydrates: 4‐C‐Formyl Branched Octoses with Structural Analogy to Bradyrhizose

2019

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The synthesis of three 4‐C‐formyl branched octoses with variable stereoconfiguration at the C‐2 and C‐3 stereogenic centers is described. This class of compounds is of interest due to potential structural analogies to the naturally occurring bradyrhizose monosaccharide. Branched key sugar intermediates of the synthesis are 2‐C‐(1,2,3‐trihydroxyprop‐1‐yl)‐β‐d‐mannosides. A new mild oxidation protocol using known TEMPO/trichloroisocyanuric acid in ethyl acetate/toluene, buffered with 3‐(N‐morpholino)propanesulfonic acid, is described as a valuable reaction for selective primary alcohol oxidation and, hence, the formation of 2‐(spirofuranose)pyranoses. Upon global deprotection these spirofuranoses give complex mixtures of diverse hemiacetal forms of the liberated 4‐C‐formyl octoses. As revealed by detailed NMR studies, the bradyrhizose‐type annulated forms do not represent the major isomers. For each of the target octoses, these potential neighboured acetal‐hemiacetal‐forms (9,7‐pyranose‐1,9‐pyranoses) seem to be unfavorable, and instead remote bis(hemiacetals) are formed (1,5‐pyranose‐9,7‐pyranoses or 1,4‐furanose‐9,7‐pyranoses) as the major species.

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Section: Resultsmentioning

confidence: 99%

Synthetic Adventures with 2‐C‐Branched Carbohydrates: 4‐C‐Formyl Branched Octoses with Structural Analogy to Bradyrhizose

2019

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“…[36,37,38] We subjected this key diol 57 to known redox isomerization conditions using Ph 3 PCl 2 . [39] Rearrangement by means of a stereospecific hydride shift was expected to provide the desired ketone. Despite various modifications of the conditions, we were unable to obtain ketone product 56 .…”

Section: Resultsmentioning

confidence: 99%

A sequential cycloaddition strategy for the synthesis of Alsmaphorazine B traces a path through a family of Alstonia alkaloids

Hong

Vanderwal

2017

Tetrahedron

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Driven by a new biogenetic hypothesis, the first total synthesis of alsmaphorazine B and several related indole alkaloids has been achieved. Numerous early approaches proved unsuccessful owing to unproductive side reactivity; nevertheless, they provided important clues that guided the evolution of our strategy. Critical to our success was a major improvement in our Zincke aldehyde cycloaddition strategy, which permitted the efficient gram-scale synthesis of akuammicine. The sequential chemoselective oxidations of akuammicine leading up to the key oxidative rearrangement also yielded several biogenetically related indole alkaloids en route to alsmaphorazine B.

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“…DeCamp et al [28] reported on the application of trimethylamine N-oxide as a stochiometric oxidant with pyridine as an additive and tert-butyl alcohol/water as the solvent at reflux temperature for the osmium tetroxide catalyzed dihydroxylation of a bicyclic trisubstituted alkene. Osmium tetroxide catalyzed syn-dihydroxylation of 7 employing standard Upjohn conditions (OsO 4 /NMO in acetone/water/tert-butyl alcohol) progressed only very reluctantly.…”

Section: Resultsmentioning

confidence: 99%

1,2‐Annulated Sugars: Synthesis of Polyhydroxylated 2,10‐Dioxadecalins with β‐manno Configuration

2016

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A new synthetic route to 1,2‐pyran‐annulated O‐glycosides (pyranopyrans) with β‐manno configuration is presented. Starting from a benzyl‐protected allyl β‐2‐uloside obtained by C2‐oxidation from the corresponding allyl glucoside, vinylation and ring‐closing metathesis provided a bicyclic alkene as a key substrate. Optimized reaction conditions involving the 2‐uloside were required to circumvent the formation of the unwanted 3,2‐enolone. Subsequent stereoselective alkene dihydroxylations were investigated and are presented. Diastereoselective catalytic osmoylation afforded the bicyclic β‐mannoside with syn‐diol configuration. In contrast, a sequence featuring a directed vanadium‐catalyzed alkene epoxidation and epoxide opening provided the corresponding 2,10‐dioxadecalin target compound with trans‐diol configuration. X‐ray crystallography was employed to study the molecular structure of the target compound with syn‐diol configuration. In addition, the molecular packing and hydrogen‐bonding interactions of the hydroxy‐rich molecule were examined.

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Novel synthesis of mevinolin-related compounds. Large-scale preparation of HMG-CoA reductase inhibitor L-679,336

Cited by 30 publications

References 0 publications

Synthetic Adventures with 2‐C‐Branched Carbohydrates: 4‐C‐Formyl Branched Octoses with Structural Analogy to Bradyrhizose

Synthetic Adventures with 2‐C‐Branched Carbohydrates: 4‐C‐Formyl Branched Octoses with Structural Analogy to Bradyrhizose

A sequential cycloaddition strategy for the synthesis of Alsmaphorazine B traces a path through a family of Alstonia alkaloids

1,2‐Annulated Sugars: Synthesis of Polyhydroxylated 2,10‐Dioxadecalins with β‐manno Configuration

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