Pyrrolidine alkaloids are made from the amino acid ornithine

Pyrrolidine is the simple five-membered cyclic amine and pyrrolidine alkaloids such as nicotine contain this ring. All are made in nature from ornithine. Ornithine is an amino acid not usually found in proteins (it’s one carbon atom shorter than lysine) but most organisms use it, often in the excretion of toxic substances. If birds are fed benzoic acid (PhCO₂H) they excrete dibenzoyl ornithine. When dead animals decay, the decarboxylation of ornithine leads to putrescine, the smell of rotten meat.

Biosynthetic pathways are usually worked out by isotopic labelling of potential precursors and in the schemes below the isotopically labelled atom is shown with a coloured blob. Some plants—notably the coca plant—produce the simple pyrrolidine alkaloid hygrine, which we will take as an illustration. If ornithine is made with a 14C label at its α position and fed to the plant, labelled hygrine is isolated. If each amino group in ornithine is labelled in turn with 15N, the α amino group is lost but the γ amino group is retained.

Further labelling experiments along these lines showed that the CO₂H group as well as the α amino group was lost from ornithine and that the rest of the molecule makes the pyrrolidine ring. The three-carbon side chain in hygrine comes from acetate, or rather from acetyl CoA, and the N-methyl group comes from (S)-adenosyl methionine. Labelling studies such as these tell us the origin of the atoms in the natural product, and we can now work through the biosynthesis—how the molecule is put together from those precursors. The first step is a pyridoxal-catalysed decarboxylation of ornithine.

Now the terminal amino group is methylated by SAM and the secondary amine cyclizes onto the pyridoxal imine to give an aminal. Decomposition of the aminal the other way round expels pyridoxamine and releases the salt of an electrophilic imine.

The rest of the hygrine structure comes from two molecules of acetyl CoA. We saw earlier in this chapter that the thiol ester is a good electrophile and also enolizes easily. We need both reactivities now in a Claisen ester condensation of acetyl CoA. The new keto-ester is very like the acetoacetates make stable enolates and the CoA thiol ester will exist mainly as its enol, stabilized by conjugation.

The cell has a good stock of acetyl CoA and its condensation product, and as soon as the iminium ion above is generated, it is attacked by the acetoacetyl CoA. All that remains to form hygrine is the hydrolysis of the CoA thiol ester and decarboxylation of the keto-acid. This is standard chemistry, but you should ensure that you can draw the mechanisms for these steps.

Tropinone is made from hygrine and it is clear what is needed. The methyl ketone must enolize and it must attack another iminium ion resembling the first but on the other side of the ring. A biological oxidant such as NADP is needed.

اخر الاخبار

اخبار العتبة العباسية المقدسة

خدمات فكرية وثقافية عديدة قدمها مركز مُلتقى القمر الثقافي لزائري الأربعين

إحياءً لذكرى زيارة الأربعين.. العتبة العباسية المقدسة تواصل إقامة مجلسها العزائي

عبر كاميرات تعمل بالذكاء الاصطناعي.. قسم الاتصالات يوضح تفاصيل جديدة حول آلية عدِّ زائري الأربعين

شعبة الخطابة الحسينية النسوية تواصل نشاطاتها الفكرية والثقافية في مجمع الشيخ الكليني

المزيد

الآخبار الصحية

حجم جزء محدد من الجسم يعكس الصحة العامة ومخاطر الأمراض

تفشي عدوى بكتيرية بفرنسا يحتمل ارتباطها بنوع من الجبن الطري

دراسة حديثة تكشف ما تفعله الشاشات بـ"قلوب الأطفال" !

متلازمة المبنى المريض.. هكذا يتحول تكييف الهواء إلى خطر صحي ؟؟

المزيد

الآخبار التكنلوجية

كيف تتعامل مع حرارة الطقس أثناء القيادة؟

لماذا يجب عليك إيقاف تكييف السيارة قبل إطفاء المحرك؟

دراسة تكشف سببا محتملا وراء زيادة خطر إصابة الأطفال بالتوحد

تشيلي.. العثور على متحجرة حيوان ثديي صغير من زمن الديناصورات

المزيد

مواضيع ذات صلة

Alkaloids are made by amino acid metabolism

The shikimic acid pathway

Phosphoenolpyruvate

Nature’s enolate equivalents: lysine enamines and coenzyme A

Reductive amination in nature

Nature’s NaBH4 is a nucleotide: NADH or NADPH

Oil and water do not mix

Lipids

Most sugars are embedded in complex carbohydrates

Glycosides in nature

Sugars can be fixed in one shape by acetal formation

Sugars normally exist in cyclic forms with much stereochemistry