Samarium Iodide-Mediated Reformatsky Reactions for the Stereoselective Preparation of β-Hydroxy-γ-amino Acids: Synthesis of Isostatine and Dolaisoleucine

Nelson, Christopher G.; Burke, Terrence R.

doi:10.1021/jo202091r

Cited by 18 publications

(16 citation statements)

References 20 publications

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“…Unfunctionalized resin was capped with a solution of acetic anhydride (10:10:80 v/v Ac 2 O: DIEA: DMF) at room temperature (1 h), then washed thoroughly with DMF to yield Resin 1 . This resin was Fmoc-deprotected with 20% piperidine in DMF (2 mL × 20 min × 2 times), then agitated with a freshly prepared solution of Fmoc-Dap-OH (Doronina et al, 2009; Nelson and Burke, 2012) (1.5 equiv), HATU (1.5 equiv), HOBt (1 equiv) and DIEA (4 equiv) in DMF (1.5 mL) at room temperature (overnight) to yield Resin 2 . Resin 2 was Fmoc-deprotected with 20% piperidine in DMF (2 mL × 20 min × 2 times), then agitated with a freshly prepared solution of Fmoc-Dil-OH (Doronina et al, 2009; Nelson and Burke, 2012) (1.5 equiv), HATU (1.5 equiv), HOBt (1 equiv) and DIEA (4 equiv) in DMF (1.5 mL) at room temperature (overnight) to yield Resin 3 .…”

Section: Star Methodsmentioning

confidence: 99%

“…This resin was Fmoc-deprotected with 20% piperidine in DMF (2 mL × 20 min × 2 times), then agitated with a freshly prepared solution of Fmoc-Dap-OH (Doronina et al, 2009; Nelson and Burke, 2012) (1.5 equiv), HATU (1.5 equiv), HOBt (1 equiv) and DIEA (4 equiv) in DMF (1.5 mL) at room temperature (overnight) to yield Resin 2 . Resin 2 was Fmoc-deprotected with 20% piperidine in DMF (2 mL × 20 min × 2 times), then agitated with a freshly prepared solution of Fmoc-Dil-OH (Doronina et al, 2009; Nelson and Burke, 2012) (1.5 equiv), HATU (1.5 equiv), HOBt (1 equiv) and DIEA (4 equiv) in DMF (1.5 mL) at room temperature (overnight) to yield Resin 3 . Resin 3 was Fmoc-deprotected with 20% piperidine in DMF (2 mL × 20 min × 2 times), then agitated with a freshly prepared solution of Fmoc-Val-OH (5 equiv), HATU (5 equiv), HOBt (1 equiv) and DIEA (10 equiv) in DMF (1.5 mL) at room temperature (3 h) to yield Resin 4 .…”

Section: Star Methodsmentioning

confidence: 99%

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Stable and Potent Selenomab-Drug Conjugates

Nelson

Nair

et al. 2017

Cell Chemical Biology

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Summary Selenomabs are engineered monoclonal antibodies with one or more translationally incorporated selenocysteine residues. The unique reactivity of the selenol group of selenocysteine permits site-specific conjugation of drugs. Compared to other natural and unnatural amino acid and carbohydrate residues that have been used for the generation of site-specific antibody-drug conjugates, selenocysteine is particularly reactive, permitting fast, single-step, and efficient reactions under near physiological conditions. Using a tailored conjugation chemistry, we generated highly stable selenomab-drug conjugates and demonstrated their potency and selectivity in vitro and in vivo. These site-specific antibody-drug conjugates built on a selenocysteine interface revealed broad therapeutic utility in liquid and solid malignancy models.

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Section: Star Methodsmentioning

confidence: 99%

Section: Star Methodsmentioning

confidence: 99%

Stable and Potent Selenomab-Drug Conjugates

Nelson

Nair

et al. 2017

Cell Chemical Biology

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“…On increasing the size at the terminal branching [i.e., (2 S )‐butyl substituent 2f ] the conversion decreased to 68%. The corresponding adduct, (4 R ,5 S ,6 S )‐ 4f , is a valuable precursor of dolaisoleucine and isostatin . Similarly, electrophile 2e , which has one methylene group between the α‐position and the branch point, and 2h , a β‐amino aldehyde, both with lower steric demand near the carbonyl group, were converted in 51–61% yields.…”

Section: Resultsmentioning

confidence: 99%

“…Hence, YfaU might be particularly useful for accepting a wide structural variety of electrophiles. Among them, N ‐protected‐amino aldehydes are particularly attractive since the aldol adducts obtained, N ‐Cbz‐amino‐4‐hydroxy‐2‐keto acid (Cbz=benzyloxycarbonyl), can be valuable intermediates for the preparation of new proline, pipecolic acid and pyrrolizidine‐3‐carboxylic acid derivatives as well as β‐hydroxy‐γ‐amino acids, for example, dolaisoleucine, isostatin and statin . Thus, our goal was to evaluate the selectivity of YfaU towards structurally diverse amino aldehydes derived from amino acids (Scheme ) to prepare novel product families.…”

Section: Introductionmentioning

confidence: 99%

2‐Keto‐3‐Deoxy‐l‐Rhamnonate Aldolase (YfaU) as Catalyst in Aldol Additions of Pyruvate to Amino Aldehyde Derivatives

et al. 2017

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4-Hydroxy-2-keto acid derivatives are versatile building blocks for the synthesis of amino acids,h ydroxy carboxylic acids andc hiral aldehydes. Pyruvate aldolasesa re privileged catalysts for as traightforward access to this class of keto acid compounds.I nt his work, aC lass II pyruvate aldolase from Escherichia coli K-12, 2-keto-3-deoxy-lrhamnonate aldolase (YfaU), was evaluated for the synthesiso fa mino acid derivatives of proline,p ipecolic acid, andp yrrolizidine-3-carboxylic acid. The aldol addition of pyruvate to N-protected amino aldehydes wast he key enzymatic aldola ddition step followed by catalytic intramolecular reductivea mination. Thec orresponding N-Cbz-amino-4-hydroxy-2-keto acid (Cbz = benzyloxycarbonyl) precursors were obtained in 51-95% isolated yields and enantioselectivity ratios from 26:74 to 95:5, with chiral asubstituted N-Cbz-amino aldehydes.( S)-N-Cbzamino aldehydes gavea ldol adducts with preferentially (R)-configuration at the newly formed stereocenter, whereas the contrary is true for (R)-N-Cbzamino aldehydes.A ddition reactions to achiral amino aldehydesr enderedr acemic aldol adducts. Molecular models of the pre-reaction ternary complexesY faU-pyruvate enolate-acceptor aldehyde were constructed to explain the observeds tereochemical outcome of the reactions.C atalytic reductive amination of the aldol adducts yielded 4-hydroxy-2-pipecolic acid, and unprecedented C-5 substituted4 -hydroxyproline andp yrrolizidine-3-carboxylic acid derivatives.Keywords: aldol reaction; amino acids;a mino aldehydes; asymmetric catalysis;b iocatalysis; biotransformations;pyruvate aldolases Introduction 4-Hydroxy-2-keto acid derivatives are versatile building blocks for the synthesiso fa mino acids,h ydroxy carboxylic acids anda ldehydes among others.[1] Biocatalytic access to 4-hydroxy-2-ketoa cid moiety can be accomplished by means of pyruvate utilizing aldolases.[2]Pyruvate-dependent aldolases are ac lass of lyases that operate in sugar acid metabolism where they utilize pyruvatea st he common aldoln ucleophilic component. Practically all enzymes are type I( i.e., enamine intermediate as nucleophilic species) but there exist also some type II enzymes (i.e., metal cofactor, enolaten ucleophile) that have received less attention from the synthetic point of view.[3] Most of the Class I pyruvate-dependent aldolases,s uch as neuraminic acid aldolase (NeuAc), 2-keto-3-deoxy-6-phospho-dgluconate (GlcA) and 2-keto-3-deoxy-6-phospho-dgalactonate aldolases( GalA), usually have as tringent selectivity for the pyruvaten ucleophile and rather broad electrophiles electivity.H owever, only electrophiles equali ns ize or larger than aldopentoseso r phosphorylated short-chain aldehydes were substrates, whereasp olar, unphosphorylated short-chain aldehydesa re converted at low reaction rates and simple aliphatic or aromatica ldehydes are not substrates. [1a,4] Va riantso ft hese enzymes were identified with remarkable selectivity and catalytic efficiency for an umber of unnaturals ubstrates,a lthough st...

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“…SmI 2 ‐promoted Reformatsky reactions were employed for the preparation of β‐hydroxy‐γ‐amino acids, such as N ‐Boc‐isostatine ( 74 ; Boc = tert ‐butoxycarbonyl) and N ‐Boc‐Dil ( 78 ; Scheme ) . The addition of aldehyde 71 to α‐chloroacetyloxazolidinone 72 , with three equivalents of SmI 2 , resulted in the formation of secondary alcohol 73 as a single diastereomer.…”

Section: Reformatsky‐type Reactionmentioning

confidence: 99%

Recent Developments in Samarium Diiodide Promoted Organic Reactions

Gopalaiah

Kagan

2013

The Chemical Record

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In the early eighties, we introduced samarium diiodide for the transformation of various functional groups. Since then, this reducing agent has been extensively used for the reductive cleavage of single bonds, C-C bond formations, C-N bond formations, and β-elimination reactions. In this Personal Account, we highlight our initial results, as well as some of the contributions from various research groups. Because of space limitations, we arbitrarily select some useful results that have recently been described in literature.

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Samarium Iodide-Mediated Reformatsky Reactions for the Stereoselective Preparation of β-Hydroxy-γ-amino Acids: Synthesis of Isostatine and Dolaisoleucine

Cited by 18 publications

References 20 publications

Stable and Potent Selenomab-Drug Conjugates

Stable and Potent Selenomab-Drug Conjugates

2‐Keto‐3‐Deoxy‐l‐Rhamnonate Aldolase (YfaU) as Catalyst in Aldol Additions of Pyruvate to Amino Aldehyde Derivatives

Recent Developments in Samarium Diiodide Promoted Organic Reactions

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