Silvia Cardani

University of Milan | UNIMI · Department of Medical Biotechnology and Translational Medicine

PHOX2B is a transcription factor essential for the development of different classes of neurons in the central and peripheral nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensit...

The central CO 2 -chemoreflex is crucial in regulating breathing, providing stimulation at rest and during challenges to homeostasis. The retrotrapezoid nucleus (RTN), located in the ventral brainstem, is essential to this process. Impaired RTN function is linked to hypoventilation syndromes, including congenital central hypoventilation syndrome (C...

PHOX2B is a transcription factor essential for the development of different classes of neurons in the central and peripheral nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensit...

PHOX2B is a transcription factor essential for the development of the autonomic nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensitivity and life-threatening sleep-related hypo...

PHOX2B is a transcription factor essential for the development of the autonomic nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensitivity and life-threatening sleep-related hypo...

Heterozygous mutations of the transcription factor PHOX2B are responsible for Congenital Central Hypoventilation Syndrome, a neurological disorder characterized by inadequate respiratory response to hypercapnia and life-threatening hypoventilation during sleep. Although no cure is currently available, it was suggested that a potent progestin drug p...

Congenital Central Hypoventilation Syndrome (CCHS) is a rare disorder of the autonomic nervous system (ANS), characterized by inadequate control of autonomic ventilation and global autonomic dysfunction. Heterozygous polyalanine repeat expansion mutations in exon 3 of the transcription factor Paired-like homeobox 2B (PHOX2B) gene occur in 90% of CC...

Neuroinflammation and cholinergic dysfunction, leading to cognitive impairment, are hallmarks of aging and neurodegenerative disorders, including Alzheimer’s disease (AD). Acetylcholinesterase inhibitors (AChEI), the symptomatic therapy in AD, attenuate and delay the cognitive deficit by enhancing cholinergic synapses. The α7 nicotinic acetylcholin...

Congenital central hypoventilation syndrome (CCHS) is a genetic disorder of neurodevelopment, with an autosomal dominant transmission, caused by heterozygous mutations in the PHOX2B gene. CCHS is a rare disorder characterized by hypoventilation due to the failure of autonomic control of breathing. Until now no curative treatment has been found. PHO...

The α7 nicotinic acetylcholine receptor (CHRNA7)modulates the inflammatory response by activating the cholinergic anti-inflammatory pathway. CHRFAM7A, the human-restricted duplicated form of CHRNA7, has a negative effect on the functioning of α7 receptors, suggesting that CHRFAM7A expression regulation may be a key step in the modulation of inflamm...

Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare life-long genetic disorder characterised by the failure of autonomic control of breathing. It is known to be caused by heterozygous mutations in the PHOX2B transcription factor, although the underlying mechanism is still unclear, and no pharmacological treatment has yet prov...

Heterozygous mutations in the PHOX2B gene are causative of Congenital Central Hypoventilation Syndrome (CCHS), a neurocristopathy characterised by defective autonomic control of breathing due to the impaired differentiation of neural crest cells (NCCs). Among PHOX2B mutations, polyalanine (polyAla) expansions are almost exclusively associated with...

The GET (Guided Entry of Tail-Anchored Proteins)/TRC (Transmembrane Recognition Complex) pathway for tail-anchored (TA) protein targeting to the ER has been characterized in detail in yeast, and is thought to function similarly in mammals, where the orthologue of the central ATPase, Get3, is known as TRC40 or Asna1. Get3/TRC40 function requires an...

NMR studies proved that cationic species are intermediates in the acid catalyzed reaction of norephedrine-derived oxazolidanes with nucleophiles. Information was gathered on the electronic structure of the cations and its dependence on ring substitution.

Pharmacologically interesting trans β-lactones 11 and 16 were synthesized using a titanium tetrachloride-mediated enantioselective aldol reaction as the key synthetic step (see Scheme 2).

A diastereo and enantioselective synthesis of compound 11 a potential useful intermediate for the lactone portion of mevinolin and compactin was developed. Our strategy is based on the high stereoselective Michael addition of alkoxide to chiral norephedrine-derived oxazolidine 4.

Polyoxygenated C4 synthons 5-7 are synthesized in enantiomerically pure form starting from ephedrine derived oxazolidines 2,4 and 13. The 1,4-benzylate addition to 2 and 4, the key step in the synthesis of 5 and 6, proceeds cleanly with almost complete diastereoface selection. The key steps in the synthesis of target 7 are the nucleophilic epoxidat...

A diastereo- and enantioselective approach to the functionalized lactam (IX) uses the KOCl epoxidation of the chiral norephedrine-derived oxazolidine (I) and the Me2CuLi addition to the product (II) as key step both proceeding regio- and stereoselectively.

Lewis acid catalyzed reaction of silylenolethers with 1 followed by a straightforward nondestructive removal of the chiral auxiliary affords the corresponding aldehydes in good e.e. Compound 1 represents the first effective chiral synthetic equivalent of formyl cation.

A diastereo- and enantioselective approach to functionalized 3,4--β-lactams 9 and 16 was developed based on the use of chiral norephedrine-derived oxazolidines. The key-steps in the synthesis of 9 (Scheme 1) are the potassium hypochlorite epoxidation of aldehyde 1 and the lithium dimethylcuprate addition to acid 2, both steps proceed regio- and ste...

The fumaraldehyde bisacetal (I) undergoes protection of one of its keto functions with the optically active norephedrine derivative (II) to give the unsaturated carbonyls (IV).

The target compound, the anti aldehyde (IX), is synthesized starting from the aldehyde (I) which, in turn, is readily available from (1R,2S)-norephedrine.

Both anti and syn enantiomerically pure functionalized α -amino-β-hydroxy acids and derivatives were synthesized starting from norephedrine-derived oxazolidine (1). The key-steps of the synthesis were the nucleophilic epoxidation of (1) and the nucleophilic opening of epoxy acid (3) with ammonia, both reactions proved regio- and diastereospecific....

Cuprate reagents in the presence of trimethylchlorosilane add with excellent Tr-face selectivity and yield to α,β-unsafcurated ketone and aldehyde bearing In γ-position a masked aldehyde represented by the C-2 of a norephedrine-derlved oxazolidine. The title compounds are obtained in high enantlomeric excess after removal of the chiral auxiliary an...

The catalytic osmylation of electron-poor allylic ethers and alcohols was studied. In the case of γ-alkoxy E-enoates reaction selectivity was found to range from 2:1 to 8:1 in favor of the (2,3-syn - 3,4-anti) product, regardless of the double bond substitution. Lower (if any) selectivity was found for the Z-isomers. On the contrary, 2-Mthylene-3-h...

The catalytic osmylation of the allyl ethers (I) or (IV) the synthesis of which is described yields the isomeric products (II) + (III) or (V) + (VI), respectively, with a general selectivity in favor of the arabino (2,3-syn-3,4-anti) configuration ((II), (Va)).

A study on the stereochemistry of the acid-catalyzed cyclization between N-protected norephedrine and α,β-unsaturated dimethyl acetals to give the title compounds is reported. Such heterocycles, on the basis of their different formation and reactivity behavior, are best classified as type I and type II oxazolidines, bearing electron-rich or -poor o...

Enantiomerically pure t-Butyl 2-amino-2,5-dideoxy---pentanoate 4c is synthesized via the highly diastereoselective MgBr2 mediated addition of dibenzylamino acetate silylketene acetal 2 to O-benzyl lactic aldehyde 3. The synthesis of γ-lactone 5c, a known intermediate in the synthesis of L-daunosamine and L-vancosamine, is also described.

The stereochemistry of the reaction between the ketene silyl acetals (I) and the aldehydes (II) in the presence of Lewis acids, especially MgBr2, is investigated.

Reaction of the aldehyde (I) with the enolate derived from (II) gives a mixture of all four diastereomers (III)-(VI).

The optically active oxazolidines (III), derived from benzyloxycarbonylnorephedrine (I) and the acetal (II) as decribed in the literature, react with the cuprates (IV) to form the products (V) of conjugate addition with high π-face selectivity.

The synthesis of threo-(VIa) and erythro-β-hydroxy-L-glutamine (VIb) from the vinyl glycine derivative (I) is described.

The MgBr2-mediated addition of 2- or 3-(methylthio)-substituted ketene silyl acetals 3 and 4 to α-alkoxy and α,β-dialkoxy aldehydes, followed by oxidation and elimination of methanesulfenic acid, gave 3,4-syn 2-methylene-3-hydroxy-4-alkoxy esters 9 and 11 with very high stereoselectivity (up to 100:1) and in good chemical yields. The same diastereo...

Cuprate reagents add to ester 2 with excellent π-face selectivity (≥95:5) and furnish the title compounds in high enantiomeric excess after removal of the chiral auxiliary.

Aus den Keten-acetalen (I) erhält man mit den Aldehyden (II) bzw. (VI) über Addukte wie (III) durch Periodat-Abbau die isomeren ungesättigten Alkohole (IV) und (V) bzw. (VII) und (VIII).

MgBr2 mediated addition of Methyl α-methylthio propionate silylketene acetal to α and α,β-alkoxy aldehydes is highly 3,4 -selective (18:1). -α- methylene-β- hydroxy-∂-alkoxy esters (6) and (8) are synthesized.

Thiopropionsäureester (I) liefert über die Enolborate (II) mit den Aldehyden (III) die syn-Addukte (IV), während über die Silylenolether (V) mit (III) in Gegenwart von Bortrifluorid die anti-Alkohole (VI) erhalten werden.

Die bei der Addition des optisch aktiven Sul?nylhydrazons (I) an die (im ?berschu? eingesetzten) racemischen Aldehyde (II) als Diastereomerengemische anfallenden Alkohole (III) werden direkt zu den ?-Hydroxy-hydrazonen (IV) desulfuriert.

In einer Eintopfreaktion wird der Thioester (I) über die isomeren Titelborane (II) und (III) (Verhältnis abhängig von Reaktionstemp.) mit den Aldehyden (IV) stereokonvergent überwiegend in die Aldolkon- 31 densationsprodukte (V) mit syn-Form übergeführt.

Optically active γ-methyl-β-hydroxy and γ-alkoxy-β-hydroxy ketones have been obtained by condensing chiral racemic aldehydes with chiral α-sulphinyl hydrazones. Good to excellent enantioselectivity and diastereoselectivity, both strongly dependent on the nature of the substrates and the reaction conditions, were achieved. The absolute and relative...

A detailed Investigation of the enolization of phenyl thiopropionate with ethylenechloroboronate (ECB) and diisopropylethylamine (DPEA) and the subsequent aldol condensations of these enolates was conducted. Alkenyloxy dialkoxyboranes derived from thioesters were found to be stereoconvergent: both Z and E enolates give syn aldol condensation produc...

Enolboronates, new enolates directly accessible from carbonyl compounds, exhibit extraordinary high erythro diastereoselection both with aliphatic and aromatic aldehydes.

R)-Gingerol (VI) wird aus dem Hydrazon (I) über das chirale Sulfoxid (II) gemäß Formelschema hergestellt.

Aus den Ethylketonen (I) erhält man mit dem Chlorboronester (II) in Gegenwart von Diisopropyl-ethyl-amin den Enolester (III), der mit Aldehyden (IV) in sterisch weitgehend einheitlicher Reaktion zu den erythro-Ketolen (V) führt.