Porantherine

A mulristrategic retrosynthetic analysis of porantherine is outlined in Section 6.2 of Part One. 

The intermediate A was also made by an alternative route using interesting new methodology for stereocontrol (Ref. 2). 

The importance of biotin in nutrition and increasing commercial needs combine to suggest the need for short and economical synthesis. Rctrosynthetic analysis using cysteine as SM goal suggested a number of synthetic pathways for study, one of which has been demonstrated as shown below. 

Methoxatin, now known as coenzyme PQQ, was originally obtained from methylotrophic bacteria but is now known to be a mammalian cofactor, for example, for lysyl oxidase and dopamine P-hydroxylase. The first synthesis of this rare compound was accomplished by the route outlined below. In the retrosynthetic analysis both of the heterocyclic rings were disconnected using directly keyed transforms. 

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Poly (vinyl pyrrol idones) polymerization, 1, 271 Polyviologens synthesis, 1, 286 Pomeranz-Fritsch synthesis isoqutnolines, 2, 428 6, 218 Pongapin synthesis, 4, 710 Poranthericine, 4, 494 ( )-Porantherine synthesis, 2, 377 Porphin, 4, 386 structure, 4, 378 Porphin, mcso-aryltri-p-tolyl-synthesis, 4, 230 Porphin, mcso-tetraalkyl-synthesis, 4, 230 Porphin, mcso-tetraaryl-synthesis, 4, 230 Porphin, mcso-tetraferrocenyl-synthesis, 4, 230 Porphin, meso-tetraphenyl-synthesis, 7, 767 Porphobilinogen biosynthesis, 1, 100... 

Observe too that, on its right, there is a window with a " 1" in a box. The synthesis tree will appear in this window as we generate it. In the upper part of this window you can read "Synt. tree of Porantherine". 

Clicking "Yes" tells the program to continue trying to disconnect porantherine. 

The program also allows you to see the bridgeheads (for polycyclic bridge systems), core bonds and strategic bonds of the active molecule. You must enter the appropriate menus "See bridgehead sites," "See core bonds," and "See strategic bonds" Process menu). Examples of the application of these options to the porantherine molecule are shown ... 

Draw the structures of twistane, tropinone, exo-brevicomin, patchouli alcohol, longifolene, sativene, luciduline and porantherine and search bifunctional relationships, rings, synthetically significant rings, bridgeheads, core bonds and strategic bonds of each one of them. 

Process automatically the structure of the alkaloid porantherine, first with the "default-order" of disconnections and then giving priority to "consonant" over "rings" disconnections. In the latter case you should "Save" only the intermediate precursors leading to the same synthetic sequence and the same starting material (A) used in Corey s synthesis, which was actually found by LHASA (see ref. 19, Chapter 12). 

The addition of acid to Az-piperideine results in an iminium ion that readily reacts with nucleophilic species. This reaction has been particularly useful for the formation of carbon-carbon bonds in alkaloid total synthesis. For example, key steps in the total synthesis of ( )-porantherine (equation 36) (74JA6517), coccinelidine (equation 37) (77H(7)685) and eburnamonine (equation 38) (65JA1580) were acid-catalyzed ring closures between A2-piperideine derivatives and ends. Even the weakly nucleophilic carbon-carbon double bond can participate in this type of reaction (80JA5955), as has been demonstrated by a recent total synthesis of a morphinan derivative (Scheme 13). 

Systematic bond disconnection of porantherine [151] with recognition of the double bond-carbonyl equivalence for synthesis generated a synthetic pathway which is based on two intramolecular Mannich reactions. The symmetrical nature of the amino diketone precursor identified by the retrosynthetic analysis facilitates its preparation and subsequent transformations. Moreover, all the hetero atoms (donors) are separated by odd-numbered carbon chains and such arrangements are most amenable to normal modes of assembly. 

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