Allyltrichlorostannane Additions to α‐Amino Aldehydes: Application to the Total Synthesis of the Aspartyl Protease Inhibitors L‐682,679, L‐684,414, L‐685,434, and L‐685,458

Dias, Luiz C.; Díaz, Gaspar; Ferreira, Andréa A.; Meira, Paulo R. R.; Ferreira, Edı́lson

doi:10.1002/chin.200324243

Cited by 8 publications

(14 citation statements)

References 24 publications

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“…The synthesis of (2-aminoacetyl)phosphoramidic acid inhibitors, such as compounds 29 and 30 (Figure 2), is outlined in Scheme 3. The amides of L-phenylalanine 34 and αphenylglycine 35 were synthesized according to literature procedures, and their reaction with the thienopyrimidine scaffold was achieved via S N Ar to give the primary amides 63 and 65. These intermediates were subsequently treated with tetrabenzyl pyrophosphate in the presence of t-BuOLi to afford the respective phosphoroamidates.…”

Section: ■ Chemistrymentioning

confidence: 99%

Pharmacophore Mapping of Thienopyrimidine-Based Monophosphonate (ThP-MP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase

et al. 2017

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The human farnesyl pyrophosphate synthase (hFPPS), a key regulatory enzyme in the mevalonate pathway, catalyzes the biosynthesis of the C-15 isoprenoid farnesyl pyrophosphate (FPP). FPP plays a crucial role in the post-translational prenylation of small GTPases that perform a plethora of cellular functions. Although hFPPS is a well-established therapeutic target for lytic bone diseases, the currently available bisphosphonate drugs exhibit poor cellular uptake and distribution into nonskeletal tissues. Recent drug discovery efforts have focused primarily on allosteric inhibition of hFPPS and the discovery of non-bisphosphonate drugs for potentially treating nonskeletal diseases. Hit-to-lead optimization of a new series of thienopyrimidine-based monosphosphonates (ThP-MPs) led to the identification of analogs with nanomolar potency in inhibiting hFPPS. Their interactions with the allosteric pocket of the enzyme were characterized by crystallography, and the results provide further insight into the pharmacophore requirements for allosteric inhibition.

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Section: ■ Chemistrymentioning

confidence: 99%

Pharmacophore Mapping of Thienopyrimidine-Based Monophosphonate (ThP-MP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase

et al. 2017

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“…Using 8 , Andricopulo et al prepared the macrolactone of migrastatin, namely MGSTA-1 . The coupling of 8 to ( E )-2,6-heptadienoic acid using DCC and DMAP [ 55 , 56 , 57 ], followed by ring-closing metathesis (RCM) [ 8 , 9 , 29 ] and removal of TBS protecting group, afforded MGSTA-1 .…”

Section: Resultsmentioning

confidence: 99%

The Therapeutic Potential of Migrastatin-Core Analogs for the Treatment of Metastatic Cancer

Giralt

2017

Molecules

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Tumor metastasis is a complex process in which cells detach from the primary tumor and colonize a distant organ. Metastasis is also the main process responsible for cancer-related death. Despite the enormous efforts made to unravel the metastatic process, there is no effective therapy, and patients with metastatic tumors have poor prognosis. In this regard, there is an urgent need for new therapeutic tools for the treatment of this disease. Small molecules with the capacity to reduce cell migration could be used to treat metastasis. Migrastatin-core analogs are naturally inspired macrocycles that inhibit pathological cell migration and are able to reduce metastasis in animal models. Migrastatin analogs can be synthesized from a common advanced intermediate. Herein we present a review of the synthetic approaches that can be used to prepare this key intermediate, together with a review of the biological activity of migrastatin-core analogs and current hypotheses concerning their mechanism of action.

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“…The ee's of compounds 7a-b after ketalization showed no appreciable changes when compared with the ee's of compounds 7a-b before the acetal hydrolysis with formic acid. It is worth noting that the very mild procedure to obtain N-protected-a-aminoaldehydes through the corresponding acetal hydrolysis without detectable racemization constitutes a valuable route to these useful chiral building blocks (Jurczak and Golebiowski 1989;Reetz 1999Reetz , 1991Gryko et al 2003;Hili et al 2008;Baktharaman et al 2008;Izawa and Onishi 2006;Garner and Park 1987;Chowdari et al 2003;Tokuyama et al 2002;Dias et al 2003;Kwon and Myers 2005;Wen and Crews 1998;Hili and Yudin 2006;Myers et al 2000;Diness et al 2004). …”

Section: Scheme 5 Tandem Oxidation and Reduction To Recycle The Unresmentioning

confidence: 99%

Resolution and absolute configuration of some α-aminoacetals: en route to enantiopure N-protected α-aminoaldehydes

Albalat¹,

Primazot²,

Wilhelm³

et al. 2011

Amino Acids

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The first successful resolution of rac-α-aminoacetals via diastereoisomeric salt formation with optically pure N-protected aminoacids is reported. The absolute configuration assignment of α-aminoacetal enantiomers is performed by an entirely non-racemizing chemical correlation method involving N-protection and a new efficient hydrolysis step followed by a reduction of the resulting N-protected α-aminoaldehyde intermediates. A racemization method of optically enriched α-aminoacetals is exemplified to allow valorisation of both enantiomers.

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Allyltrichlorostannane Additions to α‐Amino Aldehydes: Application to the Total Synthesis of the Aspartyl Protease Inhibitors L‐682,679, L‐684,414, L‐685,434, and L‐685,458

Cited by 8 publications

References 24 publications

Pharmacophore Mapping of Thienopyrimidine-Based Monophosphonate (ThP-MP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase

Pharmacophore Mapping of Thienopyrimidine-Based Monophosphonate (ThP-MP) Inhibitors of the Human Farnesyl Pyrophosphate Synthase

The Therapeutic Potential of Migrastatin-Core Analogs for the Treatment of Metastatic Cancer

Resolution and absolute configuration of some α-aminoacetals: en route to enantiopure N-protected α-aminoaldehydes

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