Carbamyl phosphate, the carbamyl donor in enzymatic citrulline synthesis1

Desymmetrization of cyclohexadienones via aza-Michael reaction catalyzed by cinchonine derived thiourea has been realized to afford a series of highly enantioenriched pyrrolidine and morpholine derivatives in excellent yields and ees. With this newly established methodology, asymmetric total synthesis of (-)-Mesembrine in high enantiomeric excess (98% ee) was accomplished.

Desymmetrization of cyclohexadienones viacinchonine derived thiourea-catalyzed enantioselective aza-Michael reaction and total synthesis of (-)-Mesembrine

An efficient, total synthesis of the Sceletium alkaloid (−)-mesembrine is accomplished in seven steps and 19% yield from a functionalized nitroalkene (itself prepared in six steps and 34% yield from ethyl 3-bromopropionate). The construction of the octahydroindole framework of mesembrine features a tandem inter [4 + 2]/intra [3 + 2] cycloaddition of a 2,2-disubstituted 1-nitroalkene and a chiral vinyl ether derived from (1R,2S)-2-(1-methyl-1-phenylethyl)cyclohexanol as the central strategic element. The two stereogenic centers of the natural product, which include a benzylic, quaternary center, were established in 26/1 selectivity in the tandem process.

Asymmetric construction of a quaternary carbon center by tandem 4 + 2/3 + 2 cycloaddition of a nitroalkene. the total synthesis of (-)-mesembrine

Publisher Summary This chapter discusses the sugars of the cardiac glycosides, which are a group of plant materials arbitrarily named because of their specific digitalis-like effect on the heart muscle. Their physiological activity is primarily dependent on the nature of the aglycon rather than on the carbohydrate component. These drugs usually consist of mixtures that are found in quite dissimilar plants, the Apocynaceae and Asclepiadaceae being especially rich in them. Chemically, the cardiac glycosides are steroid derivatives that fall into two types depending upon the aglycon. The cardiac glycosides thus defined do not all exhibit digitalis-like properties. The corresponding glycosides occur in the same plants but have not been isolated in pure form. These substances are classified with the digitaloid lactones because of analogous structures, even when they exhibit no digitalis-like activity.

The Sugars of the Cardiac Glycosides

Isolation and quantitation of picomole quantities of digoxin, digitoxin and their metabolites by high-pressure liquid chromatography.

Kfirzl ich h a b e n BOD~XDORF u n d KRIEG~R 1) aus Mesemb r y a n t h e r n u r n t o r t u o s u m L. das Alkaloid M esembr in isoliert n n d es als eine Base der Forrnel C ~ H ~ O a N beschr ieben. Nach u n s e r e n U n t e r s u c h u n g e n bes i tz t Mesernbr in die urn zwei Wasse r s toHe /irrnere Sumrnenforrnel CI~H~OaN. Das Mesernb r in [C~H~aO~N; 1Kp.0~= 186 bis 190~ [ ~ ] ~ = -5 5 , 4 ~ 0 , 5 ~ Ch lo rhydra t : C~H2sO~N-HC1; Fp. 205 bis 206~ [ a ] ~ = 8,4 • 0,5 ~ ~) en th~ l i e ine K e t o g r u p p e rni t zwei c~-st~ndigen CHe-Gruppen , zwei M e t h o x y l G r u p p e n in e inem Vera t ry l r e s t u n d e ine N-CHa-Gruppe . Die O x y d a t i o n des M esembr i n s rni t KMnO~ liefert als I I aup tp roduk t 3 ,4 -Di rne thoxypheny lg loxy l s / iu re neben Verat rumsXure . D u r c h R e d u k t i o n der K e t o g r u p p e n a c h \\u KISHNER erh~LIt m a n den G r u n d k 6 r p e r des Mesembr ins , das M e s e m b r a n : CI~H2~OoN; Kp .0 ,1= 137 bis t38 ~ I c i l y= 1 5 , 2 • Ch lo rhyd ra t : CI~H~5OeN.HC1; Fp. 193 ~ Die k a t a l y t i s c h e H y d r i e r u n g der K e t o g r u p p e des M esembr in s fiber PtO~ t f ihr t zu d e n als Mesernbrinol beze ichne ten Alkohol [C~7H~OaN; Fp. 146~ IcilY= -28,4 • 0,5~, ans dern du rch W a s s e r a b s p a l t u n g mi t t e l s P~O a in Xylo l e in Gernisch zweier isornerer Mesembrene e n t s t e h t (Chlorhydra t : CI~H~aOeN 9 HC1; Fp . 202 bis 203~ ~ ] ~ = + 5 8 , 9 • 1 7 6 D u r c h H o f r n a n n schen A b b a u erhXlt m a n aus den M e s e m b r e n e n ein e inhei t l iches D e s N M e t h y l m e s e m b r e n : ClsH~O~N; Kp.o,~ = 146 ~ ; [~]~ : 5 , 7 • ~ Der e rneu te H o f m a n n s c h e A b b a u l iefer t 3,4D i m e t h o x y d i p h e n y l (CliH~aO~; Fp. 72~ A_thylen u n d Trim e t h y l a m i n . Die Urnse t zung der K e t o g r u p p e des M esembr in s n i t Pheny l l i t h iu rn erg ib t P h e n y l m e s e m b r i n o h C2~H~9OaN; Fp . t01~ [ ~ ] ~ = + 8,3 • 0,5 ~ Die W a s s e r a b s p a l t u n g rnit SOCI~ in Benzol ff ihr t z u m P h e n y l m e s e r n b r e n (Chlorhydra t : C~H2~OeN'HC1, Fp . 235 bis 236~ [ ~ = + 6 2 , 8 • 1 7 6 B e i m H o f r n a n n s c h e n A b b a u e n t s t e h t aus P h e n y l m e s e r n b r e n das D e s N M e t h y l p h e n y l m e s e m b r e n (Chlo rhydra t : C2~H2oO~N 9 0 o t-IC1, Fp . 196 bis 197~ [ ~ = • 8 , 6 • ,5 ). D u r c h e r n e u t e n H o f m a n n s c h e n A b b a u erh~l t m a n 3,4~ O D i m e t h o x y p T e r p h e n y l (C~0HlsO 2, CH,O Fp . 158 h is 159~ A t h y l e n u n d Trim e t h y l a m i n . Auf G r u n d dieser A b b a u CH.O / ~ C H r ' \" E r g e b n i s s e s c h l a g e n w i r f i i r d a s M e s e m b r in folgende S t r u k t u r vor. Ganz offensicht l ich b e s t e h t e ine enge Bez i ehung zu der C r i n a n G r u p p e der Arnaryl l idaceen-Alkaloide~) . Das Mesembranger i i s t (I) un t e r sche ide t s ich von Cr inan (II) du rch e inen ge6f fne ten R ing :

Zur Konstitution des Mesembrins

Digoxigenin-mono- und -bis-digitoxosid, zwei neue Glykoside der Digitalis lanata

Die Struktur des mesembrins und Mesembrenins

I m Verlaufe unse re r schon sei t l~ngerer Zeit im Gange bef ind l ichen U n t e r s u c h u n g e l l fiber die Reil la lkaloide der Rauwol f i a Se rpen t ina h a b e n wir zwei lleue Stoffe aufgefulldell , die b i sher noch n i ch t besehr ieben wurden . Es h a n d e l t s ich u m zwei S u b s t a n z e n I und II , die in eiller g e m e i n s a m e n Frakt ion m i t d e m seda t iv w i rkenden Pr inz ip der Droge, d e m Reserp in , vorkommel l . Von e iner N a m e n g e b u l l g wollen wir absehen , bis ihre even tue l l e V e r w a n d t s c h a f t m i t schon bek a n n t e n Stoffen wei ter gekl/irt ist. Die p h y s i k o e h e m i s c h e n D a t e n s ind :

H. Spingler

Papers

Zur Konstitution des Mesembrins

Digoxigenin-mono- und -bis-digitoxosid, zwei neue Glykoside der Digitalis lanata

Die Struktur des mesembrins und Mesembrenins

Neue Alkaloide aus Rauwolfia Serpentina

Gitaloxin, ein neues Hauptglykosid der Digitalis purpurea