Synthesis of Nuevamine Aza-Analogues by a Sequence: I-MCR–Aza-Diels–Alder–Pictet–Spengler

Abstract

A series of nuevamine aza-analogues were prepared in moderate to good yields in two reaction steps. The synthetic strategy involves an isonitrile-based multicomponent reaction, including an aza-Diels-Alder cycloaddition and Pictet-Spengler reaction as postcondensation.

Synthesis of Tris-Heterocycles via a Cascade IMCR/Aza Diels-Alder + CuAAC Strategy

“…Using catalytic Sc(OTf) 3 under conventional heating, 6a was obtained in 42% yield (entry 5, Table 1). Microwave heating with Sc(OTf) 3 or Yb(OTf) 3 (Islas-Jácome et al, 2011, 2012) raised the yield to 69 and 62%, respectively (entries 6-7, Table 1). We therefore used the optimal conditions (entry 6: 3 mol% Sc(OTf) 3 , microwave heating 60–80 °C, 1.5 h) to synthesize the series of fused bis-heterocycles 6a - l (Table 2).…”

“…Isocyanide-based multicomponent reactions (IMCRs) are the most efficient strategies to synthesize pyrrolo[3,4- b ]pyridin-5-ones, and Zhu first reported a one-pot synthesis in 2001 (Sun et al, 2001). We synthesized various annulated polyheterocycles containing this fused bis-heterocycle via IMCR strategies (Islas-Jácome et al, 2011, 2012). However, there are no published reports of pyrrolo[3,4- b ]pyridin-5-ones linked to other heterocycles in a non-annulated fashion using IMCRs.…”

Synthesis of 2-Tetrazolylmethyl-isoindolin-1-ones via a One-Pot Ugi-Azide/(N-Acylation/exo-Diels–Alder)/Dehydration Process

“…A further experiment was performed increasing the amount of 7 to 1.5 equiv, producing 87% yield after 4 h (entry 7, Table 1). Two further experiments were performed at 110 °C under conventional or MW heating conditions, 40 but the yields obtained decreased to 68% (1 h) and 65% (0.2 h), respectively (entries 8 and 9, Table 1). A final experiment was performed using US, producing a yield of 72% in 1 h (entry 10, Table 1).…”

Ultrasound-assisted diastereoselective green synthesis of spiro-fused-γ-lactams functionalized with an amide bond heterocyclic bioisostere via the Ugi azide/domino process coupled strategy

“…There are a few reports on the use of orthogonal heterocyclic reagents in IMCRs coupled with post-transformations as efficient synthetic tools to generate high molecular diversity and complexity to access bioactive molecules containing several heterocyclic cores reported. 5 As part of our research program, we focused on synthesising peptidomimetic heterocycles like spiro-fused-γ-lactams employing orthogonal heterocyclic reagents in a UA-based strategy. 6 The IMCR using heterocyclic orthogonal reagents to access building blocks for synthesising polyheterocyclic peptidomimetics is shown in Scheme 1.…”